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THE  CONTROL  OF  HUNGER  IN 
HEALTH  AND  DISEASE 


THE  UNIVERSITY  OF  CHICAGO  PRESS 
CHICAGO,  ILLINOIS 


Bgents 
THE  BAKER  &  TAYLOR  COMPANY 

NEW   YORK 

THE  CUNNINGHAM,  CURTISS  &  WELCH  COMPANY 

LOS   ANGELES 

THE  CAMBRIDGE  UNIVERSITY  PRESS 

LONDON   AND   EDINBURGH 

THE  MARUZEN-KABUSHIKI-KAISHA 

TOKYO,  OSAKA,  KYOTO 

THE  MISSION  BOOK  COMPANY 

SHANGHAI 

KARL  W.  HIERSEMANN 

LEIPZIG 


THE 

CONTROL  OF  HUNGER 

IN    HEALTH 

AND  DISEASE 


By  ^ 

ANTON    JULIUS  JCARLSON 


mm^ 


THE  UNIVERSITY  OF  CHICAGO  PRESS 
CHICAGO,  ILLINOIS 


Copyright  1916  By 
The  University  of  Chicago 


All  Rights  Reserved 


•? 


Published  September  1916 


Composed  and  Printed  By 

The  University  of  Chicago  Press 

Chicaj;o,  Illinois,  U.S.A. 


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a  13 

nib  *^*^^^ 


PREFACE 


The  following  pages  contain  a  summary  of  the  work  on  the 
stomach,  with  special  reference  to  hunger  and  appetite,  carried  out 
in  the  Hull  Physiological  Laboratory  of  the  University  of  Chicago 
during  the  last  four  years.  We  have  aimed  to  present  this  digest 
in  the  light  of  the  entire  biological  and  clinical  literature  on  the 
subject,  hoping  that  it  may  encourage  more  intensive  work  on 
hunger  and  appetite  control,  particularly  in  the  fields  of  clinical 
medicine  and  comparative  physiology,  as  the  work  of  the  past  on 
this  problem  is  not  commensurate  with  its  biological,  medical,  and 
economic  importance. 

The  complete  analysis  of  hunger  may  not  yield  us  control  over 
the  hunger  mechanism,  but  it  is  at  least  the  most  promising  line  of 
attack.  The  scientist  will  concede  its  value  to  biology,  and  the 
physician  readily  appreciates  its  significance  for  rational  thera- 
peutics; but  the  layman  may  question  the  practical  utility  of 
hunger  control  to  society  as  a  whole,  in  view  of  the  fact  that  it  has 
played  no  role  in  past  evolution.  This  is  granted.  But  the 
elimination  of  many  biological  correctives  by  the  artificialities 
of  modern  civilization  calls  for  rational  guidance  of  all  phases  of 
human  behavior,  including  the  desire  for  food.  '  In  these  times  of 
plenty,  overfeeding,  with  its  physiological  penalties  and  economic 
waste,  is  on  the  whole  more  prevalent  than  undernutrition,  because 
of  the  barbaric  indulgence  in  the  pleasures  of  the  table  in  the 
absence  of  the  physical  stress  of  more  primitive  social  condition. 
And  when  hunger  becomes  pathologically  exaggerated  the  physi- 
cian of  today  knows  no  remedy;  when  it  fails  in  disease,  he  dis- 
penses the  "bitter  herb"  of  tradition — and  hopes  for  the  best. 
Hence,  when  the  reader  has  followed  us  through  these  we  hope 
not  too  technical  pages,  we  believe  that  he  will  agree  that  there  is 
yet  much  work  to  be  done  on  the  problem  of  hunger  control — work 
worth  doing,  co-operative  work  of  the  clinic  and  the  biological 

laboratory. 

A.  J.  Carlson 

University  of  Chicago 
September,  191 6 


343443 


TABLE  OF  CONTENTS 

CHAPTER  PAGE 

I.  The  Biological  Significance  of  Hunger       ....  i 

II.  Historical i6 

III.  The  Stomach  in  Hunger 30 

IV.  The  Stomach  in  Hunger  {Continued) 56 

V.  Some  Accessory  Phenomena  in  Hunger 84 

VI.  The  Relation  of  Hunger  to  Appetite 96 

VII.  The  Sensibility  of  the  Gastric  Mucosa       .       .       .       .  loi 

VIII.  Hunger  and  Age 119 

IX.  Hunger  in  Prolonged  Starvation 125 

X.  The  Nervous  Control  of  the  Hunger  Mechanism    .       .  149 

XI.  The  Nervous  Control  of  the  Hunger  Mechanism  {Con- 
tinued)    161 

XII.  The  Nervous  Control  of  the  Hunger  Mechanism  {Con- 
tinued) .  ^ 199 

XIII.  The  Chemical  Control  of  the  Hunger  Mechanism  .       .  217 

XIV.  Secretion  of  Appetite  Gastric  Juice  in  Man      .       .       .  232 
XV.  The  Chemistry  of  Human  Appetite  Gastric  Juice     .       .  248 

XVI.  Hunger  and  Appetite  in  Disease 261 

XVII.  Hunger  and  Appetite  in  Disease  {Continued)       ...  289 

Bibliography 303 

Index 317 


CHAPTER  I 

THE  BIOLOGICAL  SIGNIFICANCE  OF  HUNGER 

I.      HUNGER  IN  THE   UNICELLULAR  ANIMALS 

The  complex  of  sensation  that  in  man  and  the  higher  animals 
urges  and  compels  to  ingestion  of  food  is  called  hunger  and  appetite. 
From  the  standpoint  of  the  persistence  of  living  organisms  the 
ingestion  of  food  is  as  important  as  reproduction.  Consequently 
the  hunger  sensation  is  as  fundamental  as  the  urge  or  appetite  of 
sex.  In  fact,  if  we  define  hunger  biologically  as  the  conditions 
(rather  than  the  sensation  complex)  that  lead  to  taking  food,  hun- 
ger is  even  more  fundamental  or  primitive  than  the  sexual  urge 
(libido),  since  feeding  is  a  necessity  in  all  forms  of  life,  while  sexual 
reproduction  is  not. 

Whatever  be  the  underlying  mechanisms  in  the  genesis  of  the 
hunger  urge,  in  the  higher  animals  this  urge  is  obviously  a  sensa- 
tion involving  a  more  or  less  complex  nervous  organization.  Hun- 
ger as  a  sensation  or  conscious  process  is  therefore  probably  confined 
to  animals  having  a  nervous  system  and  an  alimentary  canal.  But 
all  living  organisms  feed.  What,  then,  are  the  factors  that  lead  to 
the  ingestion  of  food  in  unicellular  animals  and  in  the  simpler 
metazoa  having  no  specialized  nervous  system?  And  are  there 
any  essential  connections  between  these  primordial  factors  that 
cause  the  ameba  to  pursue  and  engulf  another  moving  protozoan, 
and  the  mechanism  of  the  hunger  urge  compelling  a  starving  wolf 
to  chase,  capture,  and  devour  a  rabbit  ? 

All  the  unicellular  animals  live,  at  least  during  their  periods  of 
activity,  in  water,  in  animal  and  plant  fluids,  or  within  the  living 
cells  of  other  animals.  In  the  case  of  the  simpler  organisms  that 
are  parasitic  the  conditions  of  feeding  are  essentially  those  of  the 
tissue  cells  of  the  higher  animals.  That  is  to  say,  the  food  materials 
are  in  solution  in  the  medium  surrounding  the  cell  or  the  animal. 
According  to  Putter,  this  also  applies  to  all  lower  forms  of  life 


2  CO.^n^ROi:  OF  IKTNGER  IN  HEALTH  AND  DISEASE 

inhabiting  the  waters  of  the  earth.  It  is  not  known  to  what  extent 
the  organic  material  in  solution  in  the  sea  water  actually  sustains 
the  lower  animal  life,  but  it  is  in  all  probability  a  very  small,  if  not 
entirely  a  negligible  factor  (Biedermann,  Lipschutz,  Kerb,  Mor- 
gulis).  We  do  know  that  all  metazoa  feed  on  other  unicellular 
animals  and  plants,  whole  or  in  fragments.  That  is,  they  take 
into  their  bodies  as  food  other  solid  bodies.  As  regards  the  actual 
processes  of  ingestion  of  solids  by  the  protozoa,  we  have  practically 
identical  conditions  in  the  case  of  the  special  phagocytic  cells  in 
the  higher  animals,  although  the  latter  is  probably  not  a  feeding 
process  primarily. 

What  determines  the  amount  and  the  avidity  of  food  ingestion 
in  the  unicellular  animals?  During  the  active  stage  the  feeding 
appears  to  be  on  the  whole  as  continuous  as  contact  with  food 
particles  permits.  Nutrient  and  non-nutrient  particles  are  taken 
up  somewhat  indiscriminately,  although  there  are  many  exceptions 
to  this  rule.  In  some  cases  minute  motile  organisms  may  by  the 
force  of  their  own  motility  penetrate  into  a  unicellular  animal  only 
to  be  digested  by  the  latter,  but  the  taking  up  of  solid  particles  by 
protozoa  is  mainly  due  to  active  ameboid  movements.  Augmenta- 
tion of  ameboid  movements,  increased  rate  of  contraction  of 
pseudopodia  acting  as  feeders,  increased  ciHary  motion  both  in 
free  swimming  and  in  sessile  forms  might  be  taken  as  external 
expressions  of  states  of  hunger  as  these  would  enhance  the  securing 
of  food. 

Are  such  expressions  of  hunger  state  actually  present?  Jen- 
nings, in  his  studies  of  the  feeding  processes  of  ameba,  is  silent  on 
this  point,  except  for  a  few  incidental  observations  that  an  ameba 
may  remain  at  rest  for  a  few  minutes  after  having  taken  up  a 
morsel  of  food,  but  since  the  ameba  is  on  the  go  again  before  this 
food  is  actually  digested,  the  brief  rest  period  cannot  be  interpreted 
as  a  state  of  satiety.  Verworn  thinks  that  all  the  phenomena  of 
feeding  in  the  protozoa,  including  a  certain  capacity  of  selection  of 
food,. involve  automatic  motility  (chemo-  and  stereotropism)  only, 
but  we  are  not  informed  whether  the  rate  of  this  motiHty  varies 
with  the  degree  of  hunger.    In  vorticella  Hodge  and  Aikens  found 


BIOLOGICAL  SIGNIFICANCE  OF  HUNGER  3 

that  the  cilia  worked  uniformly  and  continuously  night  and  day, 
in  drawing  in  and  assorting  food  particles:  "all  efforts  to  surfeit 
the  tiny  animals  with  food  produced  no  appreciable  effect  in  satis- 
fying their  apparent  hunger."  In  the  presence  of  an  abundance  of 
food  the  body  cilia  of  Paramecium  beat  less  actively,  thus  bringing 
the  animal  to  rest,  while  the  oral  cilia  continue  in  activity,  drawing 
the  food  particles  into  the  mouth  (Jennings).  Wallengren,  on  the 
other  hand,  found  no  change  in  ciliary  movements  and  vacuole 
contractions,  or  in  the  excitabihty  of  the  Paramecium  during  hun- 
ger except  that  ciliary  and  vacuole  activity  is  decreased  when  the 
organism  is  near  death  from  starvation. 

Schaeffer  has  described  in  stentor  certain  differences  in  behavior 
between  the  states  of  hunger  and  satiety.  When  stentor  is  gorged 
with  food  it  remains  somewhat  contracted,  the  activity  of  the 
membranellae  are  greatly  decreased,  the  animal  is  less  excitable  to 
external  stimuH,  and  it  discriminates  more  perfectly  between  food 
particles  and  indigestible  particles  in  the  water  current.  The 
degree  of  satiety  appears  to  depend  on  other  factors  beside  the 
amount  of  food  in  the  body.  It  seems  clear,  then,  that  a  state  of 
depletion  or  hunger  in  the  stentor  leads  to  increased  excitability, 
increased  motility,  and  increased  avidity  of  food  ingestion.  It  is 
not  unlikely  that  future  investigations  will  reveal  similar  differences 
in  most  of  the  protozoa.  Parker  found  that  meat  or  meat  extract 
reverses  the  stroke  of  the  labial  cilia  in  sea  anemones,  so  that  the 
water  current  carries  the  food  particles  into  the  esophagus.  This 
appears  to  be  an  instance  of  a  considerable  degree  of  specialization. 
Will  meat  extract  in  the  sea  water  induce  this  reversal  after  the 
anemone  is  gorged  with  meat  or  other  forms  of  food  ? 

As  regards  food  substances  in  solution,  we  may  assume  that 
the  rate  and  quantity  of  ingestion  depend  on  the  diffusion  rate  of 
the  substance  and  the  permeability  of  cell  surfaces.  Dilution  of 
food  material  within  the  cell  may  increase  surface  permeabiHty, 
and  vice  versa.  We  know  so  little  of  the  correlation  of  the  inter- 
nal processes  in  living  cells  and  unicellular  animals  that  we  cannot 
predict  what  effect  scarcity  of  nutrient  material  within  the  cell 
has  on  ameboid  and  ciliary  movements,  except  that  when  the 


4  CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

depletion  approaches  exhaustion  these  movements  probably  suffer 
depression.  In  some  animals  partial  or  complete  starvation  ap- 
pears to  accelerate  metamorphosis  and  redifferentiation,  but  the 
factors  involved  in  these  processes  are  obviously  more  complex 
than  that  of  simple  and  direct  cell  stimulation. 

In  the  ingestion  of  organic  particles  or  cells  by  the  special 
phagocytes  in  the  higher  animals,  certain  new  factors  enter  into 
play.  In  the  first  place,  phagocytosis  in  the  metazoa  is  not  pri- 
marily a  feeding  process,  but  concerned  with  destruction  of  cellular 
debris  and  cells  foreign  to  the  organism.  So  far  as  we  know,  the 
metazoan  phagocytes  feed  on  the  organic  substances  in  solution 
in  the  body  fluids,  just  like  the  cells  of  other  tissues.  Secondly, 
the  rate  and  quantity  of  ingestion  of  the  foreign  cells  depend  in 
part,  not  on  the  condition  of  the  phagocyte,  but  on  certain  sub- 
stances (opsonins)  in  the  body  fluids  that  act  on  the  foreign  cells. 
This  factor  is  not  known  to  be  involved  in  the  feeding  phagocytosis 
of  the  protozoa.  Thirdly,  even  apart  from  the  opsonin  factor,  cer- 
tain of  the  phagocytic  cells  of  the  metazoa  appear  capable  of  being 
*' trained"  to  increased  activity.  The  mechanics  of  this  capacity 
is  a  matter  of  conjecture.  These  differences  in  the  biological 
meaning  of  phagocytosis  in  the  metazoa,  and  the  feeding  phagocy- 
tosis in  the  protozoa  do  not  imply  that  the  essential  mechanics  of 
the  phagocytic  processes  in  the  two  groups  are  different. 

There  are  indications,  then,  that  relative  depletion  of  ingested 
food  material,  at  least  in  some  of  the  protozoa,  results  in  increased 
motility  (ameboid,  ciliary)  and  increased  avidity  for  food  or  rate 
of  food  intake.  These  phenomena  probably  indicate  a  condition  of 
increased  cell  excitability.  That  is  to  say,  a  state  of  hunger  in  the 
protozoa  is  a  state  of  increased  excitability.  The  question  how  a 
state  of  cell  hunger  causes  primarily  a  state  of  increased  cell  excita- 
bility cannot  be  entered  into  here.  To  those  who  prefer  anthropo- 
morphic concepts  the  pursuit,  capture,  and  selection  of  food  by 
the  protozoa  become  expressions  of  conscious  states  analogous  to 
those  in  higher  animals  under  like  conditions.  But,  for  the  present, 
at  any  rate,  simpler  explanations  are  not  only  adequate,  but  more 
useful.    The  principles  of  diffusion  and  selective  permeability  or 


BIOLOGICAL  SIGNIFICANCE  OF  HUNGER  5 

absorption  suffice  to  account  for  ingestion  of  food  in  solution. 
The  selection  of  solid  food,  so  far  as  this  principle  is  in  evidence,  is 
probably  a  matter  of  inherited  mechanism  for  differential  response 
to  chemical  and  mechanical  stimuli.  The  ameboid  and  ciliary 
motility  involved  in  the  hunger  state  introduces  more  complex 
factors.  Rhumbler  endeavored  to  analyze  the  former  into  purely 
physical  surface  tension  phenomena.  Jennings  has  shown,  at  least 
for  the  ameba,  that  the  surface-tension  theory  is  untenable.  But 
while  we  are  thus  forced  back  on  unknown  factors  in  the  organiza- 
tion of  the  cell,  there  is  no  reason  for  believing  that  when  once 
analyzed  these  cell  processes  are  not,  individually,  quite  as  definitely 
physical  and  chemical  phenomena  as  surface  tension.  Hamburger 
has  recently  shown  that  lack  of  oxygen  acts  as  a  primary  stimulus 
to  phagocytosis.  But  this  is  in  all  probability  not  the  mechanism 
that  induces  increased  cell  motility  in  state  of  cell  hunger,  as  there 
is  no  evidence  that  a  decrease  in  the  food  material  in  the  cell  is 
accompanied  by  oxygen  want. 

II.      HUNGER  IN  PLANTS 

This  general  biological  conception  of  hunger  is  probably  as 
applicable  to  the  lowest,  or  unicellular  plants,  as  to  the  unicellular 
animals.  But  we  have  been  unable  to  find  any  data  bearing  directly 
on  this  question.  We  have  extensive  studies  on  the  chemo tactic 
and  general  tropic  behavior  of  the  lower  plants  (Pfeifer,  Kniep, 
Kusano,  Shibata,  etc.).  Kniep  ascribes  senses  of  taste  and  smell 
to  bacteria,  and  shows  that  the  response  of  bacteria  to  certain 
chemical  stimuli  depends  on  the  reaction  of  the  culture  medium, 
but  he  does  not  seem  to  have  raised  the  question  whether  the 
quantity  and  quality  of  the  food  in  the  culture  medium  is  also  a 
factor  in  this  response.  Nor  is  the  question  of  the  effect  of  starva- 
tion on  the  behavior  of  bacteria  raised  in  the  recent  extensive 
studies  on  the  metabolism  of  bacteria  by  Kendall  and  his  pupils. 

The  swarm  cells  of  the  spore-producing  plants  appear  to  feed 
by  phagocytosis,  just  like  the  unicellular  animals,  and  it  is  likely 
that  this  feeding  phagocytosis  in  plants  is  influenced  by  hunger 
in  the  same  way  as  in  the  lower  animals.    Lister  describes  the 


6  CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

ingestion   of  microspores   and   bacteria   by   the   swarm   cells   of 
mycitozoa,  and  records  the  following  feeding  behavior: 

In  one  instance,  after  taking  in  two  stout  bacilli,  and  inclosing  them  in 
separate  vacuoles,  the  swarm  cell  remained  quiescent  for  a  length  of  time. 
I  watched  the  gradual  process  of  digestion  of  the  bacilli.  After  remaining 
(quiescent)  under  observation  for  nearly  an  hour  and  a  half  the  swarm  cell 
swam  off  with  vigorous  lashing  movement  of  the  cilium. 

With  the  exception  of  some  of  the  bacteria,  the  swarm  cells  of 
the  sporophytes,  the  group  of  ^^parasitic"  plants  and,  to  a  certain 
extent,  the  so-called  ''carnivorous'^  plants,  the  vegetable  organisms 
feed  primarily  on  the  inorganic  material  in  the  soil  and  on  the 
carbon  dioxide  of  the  air,  and  in  these  feeding  processes  motility 
of  the  plant,  apart  from  growth,  plays  a  minor  part.  The  plant 
cannot  move  itself,  nor  can  it  move  its  food,  even  to  the  extent  that 
both  are  possible  in  sessile  animals.  We  may  speak  with  perfect 
justification  of  starvation  in  plants,  but  in  the  case  of  the  higher 
plants  there  is  no  evidence  that  starvation  increases  excitability 
and  motility,  that  is,  induces  a  biological  state  of  hunger,  nor  would 
such  changes  aid  the  higher  plants  in  securing  food. 

III.      HUNGER  IN  THE  HIGHER  ANIMALS 

As  experienced  by  man,  the  hunger  urge  is  a  more  or  less  uncom- 
fortable feeling  of  tension  or  pressure  and  pain  referred  to  the 
region  of  the  stomach.  In  normal  persons  the  hunger  must  become 
exceptionally  strong  to  be  markedly  painful.  Ordinarily  the  feeling 
is  one  of  somewhat  uncomfortable  tension,  accompanied  by  a 
feeling  of  ''emptiness"  in  the  epigastric  region. 

Another  characteristic  element  in  the  hunger  feeling  as  known 
in  man  is  its  periodicity  or  intermittency,  even  when  the  stomach 
continues  empty  and  the  physical  activity  of  the  individual  proceeds 
without  interruption.  The  significance  of  this  attribute  has  been 
especially  emphasized  by  Bardier,  Sternberg,  Polimanti,  Cannon 
and  Washburn.  It  probably  appHes  to  the  hunger  sensation  in 
most  mammals  and  birds.  In  the  lower  animals,  so  far  investigated, 
this  periodicity  is  of  a  different  type,  or  is  possibly  lacking.  Some 
persons  appear  to  experience  a  certain  feeling  or  sensation  in  the 


BIOLOGICAL  SIGNIFICANCE  OF  HUNGER  7 

esophagus,  the  throat,  and  the  muscles  of  mastication  synchronously 
with  the  gastric  hunger.  The  writer  has  never  experienced  these 
esophagus  and  throat  elements.  From  all  accounts,  they  differ 
from  the  gastric  sensation  in  not  being  uncomfortable  or  painful. 
In  the  species  of  birds  having  a  region  of  the  esophagus  dilated 
into  a  crop,  the  hunger  sensation  probably  has  its  origin  in  the  crop 
rather  than  in  the  muscular  stomach  or  gizzard. 

The  epigastric  sensation  of  varying  degrees  of  pain  is,  however, 
the  one  indispensable  element  in  hunger.  But  frequently  certain 
accessory  phenomena  are  present.  The  most  common  of  these  is  a 
feeling  of  general  lassitude  or  weakness.  Headache,  nausea,  nervous 
irritability,  vaso-motor  instabihty,  and  even  fainting  may  appear  as 
part  of  the  hunger  complex.  Strictly  speaking,  a  certain  degree 
of  nervous  hyperexcitability  is  a  necessary  effect  of  hunger  of  even 
moderate  intensity,  and  should  therefore  not  be  called  an  accessory 
phenomenon.  But  in  normal  persons  with  stable  nervous  organi- 
zation, strong  hunger  may  be  present  without  any  feeling  of  weak- 
ness, headache,  or  obvious  manifestations  of  nervousness.  In  some 
individuals,  on  the  other  hand,  the  feeling  of  weakness,  headache, 
and  general  restlessness  may  be  so  marked  as  to  crowd  out  of 
consciousness  the  central  factor  of  hunger,  the  gastric  hunger  pangs. 

In  man  the  genesis  of  the  hunger  sensation  requires  a  stomach 
empty  or  nearly  empty  of  food.  Adult  persons  eating  three  to  five 
large  meals  per  day  probably  seldom  experience  hunger  unless 
engaged  in  severe  physical  labor  or  exposed  to  intense  cold.  In 
such  individuals  the  nervous  impulses  from  the  stomach  that  give 
rise  to  the  hunger  pangs  do  not  become  sufficiently  intense  to  affect 
consciousness. 

We  shall  show  later  that  the  genesis  of  the  hunger  pangs  is  due 
to  certain  contractions  and  tonus  states  in  the  stomach,  the  afferent 
nervous  impulses  thus  initiated  affecting  certain  parts  of  the  brain. 
Hunger  as  known  in  man  thus  requires  a  nervous  system,  a  mus- 
cular digestive  tract,  and  an  afferent  or  sensory  pathway  connecting 
the  two.  These  anatomical  conditions  are  common  to  all  verte- 
brates, and  to  the  various  invertebrate  groups  down  to  and  including 
the  coelenterates. 


8  CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

The  influence  of  the  hunger  state  on  the  behavior  is  essentially 
the  same  in  all  these  animals.  A  fundamental  characteristic  is 
increased  nervous  excitabihty  and  restlessness.  The  restlessness 
is  probably  not  primarily  due  to  the  consciousness  of  the  hunger 
feeling,  since  it  is  in  evidence  in  animals  deprived  of  their  cerebrum 
(dogs,  birds).  The  strong  hunger  urge  evidently  inhibits  fear,  as 
the  starving  animal  becomes  more  bold  and  ferocious.  It  is  gen- 
erally held  that  the  state  of  hunger  in  man  tends  to  produce  a 
cantankerous  or  unsocial  disposition.  On  the  other  hand,  pro- 
longed fasting  by  the  religious  devotee  is  supposed  to  make  him 
more  worthy  or  fit  to  commune  with  the  gods. 

In  the  normal  man,  and  probably  in  the  carnivorous  animals,  an 
empty  or  a  nearly  empty  stomach  is  a  requisite  for  the  appearance 
of  the  hunger  feeling.  This  is  evidently  not  the  case  in  the  ruminat- 
ing animals  and  in  the  herbivora  in  general,  for  in  these  animals 
the  stomach  is  never  empty — not  even  after  days  of  starvation. 
Birds,  also,  feed  more  or  less  continuously,  even  though  the  crop 
or  the  stomach  is  quite  filled  with  food.  Either  these  animals  do 
feel  hunger  on  a  partially  filled  stomach,  or  else  they  eat,  not  because 
of  feeling  the  hunger  urge,  but  because  of  appetite. 

On  the  other  hand,  hunger  may  be  apparently  absent  in  some 
animals,  even  though  the  stomach  is  completely  empty  of  food 
for  weeks  or  months.  It  is  generally  accepted  as  a  fact  that  the 
Rhine  and  the  Pacific  species  of  salmon  do  not  feed  after  entering 
the  rivers  to  spawn,  although  the  fish  is  doing  great  muscular  work 
in  going  hundreds  of  miles  against  river  currents,  in  ascending  falls, 
and  in  fighting  rivals.  Voit  thought  that  under  these  conditions 
the  fish  cannot  be  feeling  hunger.  When  in  captivity,  certain 
animals  may  refuse  food  even  to  the  point  of  starving  to  death  in 
the  presence  of  plenty.  The  call  of  the  empty  stomach,  if  suffi- 
ciently strong,  wakes  up  the  sleeping  child,  the  sleeping  man,  or 
the  sleeping  dog,  but  the  empty  stomach  does  not  appear  to  disturb 
the  hibernating  animal.  "The  caterpillar,"  says  the  great  physiolo- 
gist Haller,  "does  nothing  but  eat  and  defecate."  After  the  cater- 
pillar has  turned  into  a  butterfly  he  may  never  feed  again, 
particularly  if  his  span  of  life  is  a  short  one,  despite  great  physical 


BIOLOGICAL  SIGNIFICANCE  OF  HUNGER  9 

exertion  in  flight  and  reproduction.  It  does  not  appear  that  this 
diminution  or  absence  of  feeding  in  many  insects  after  the  final 
metamorphosis  is  associated  with  atrophy  or  absence  of  the  ah- 
mentary  tract.  These  special  conditions  obviously  involve  changes 
in  the  brain  processes,  in  the  stomach,  or  in  the  nervous  connections 
between  the  brain  and  the  stomach,  which  must  be  cleared  up  by 
new  lines  of  work;  but  they  do  not  overthrow  the  foregoing  view 
of  the  role  of  the  hunger  urge  in  feeding,  or  the  role  of  the  empty 
stomach  in  the  genesis  of  this  urge. 

Except  in  the  peculiar  and  special  cases  referred  to  above  there 
is  evidence  that  the  intensity  or  persistence  of  the  hunger  urge 
runs  parallel  with  the  degree  of  activity  and  the  rate  of  metaboHsm 
in  the  normal  individual.  Hunger  is  thus  more  marked  in  the 
young  and  growing  than  in  the  aged  and  inactive  individual. 
There  are  indications  in  mammals  that  hunger  may  be  experienced 
even  before  birth.  In  warm-blooded  animals  hunger  is  augmented 
by  external  cold,  and  depressed  by  external  heat.  The  reverse 
is  probably  true  in  the  cold-blooded  animals,  but  this  point  has 
not  been  experimentally  determined.  These  relations  do  not 
obtain  in  various  conditions  of  disease. 

IV.   HUNGER,   APPETITE,   AND   THE   INGESTION   OF   FOOD 

Why  does  this  feeling  of  uncomfortable  tension  or  hunger  pang 
in  the  stomach  induce  us  to  take  food  ?  The  obvious  reply  is  that  we 
know  that  eating  will  abolish  the  pangs.  That  is,  it  is  a  matter  of 
individual  experience.  This  answer  does  not  seem  adequate  in  the 
case  of  the  newborn  animal.  Even  if  the  animal  experienced  the 
sensation  of  hunger  before  birth,  he  cannot  have  experienced  what 
effect  the  ingestion  of  food  has  on  this  sensation.  What  induces 
the  newborn  animal  to  take  his  first  meal  ?  Is  it  a  matter  of  inherited 
reflexes  or  ''instinct"  ?  Gemelli  and  others  refer  to  hunger  as  an 
''instinct."  The  animal  emerges  from  the  egg  or  uterus  provided 
with  all  the  essential  reflexes,  the  working  order  of  most  of  these 
probably  already  tried  out  before  entering  upon  the  new  mode  of 
living.  The  feeding  reflexes  are  there;  so  are  the  defensive  ones 
in  the  way  of  rejection  of  unpalatable  or  really  injurious  substances 


lO  CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

once  in  the  mouth.  We  have  seen  that  the  hunger  state  of  the 
stomach  augments  the  reflex  excitability.  This  leads  to  greater 
degree  of  moving  about  on  the  part  of  the  newborn  animal  capable 
of  locomotion,  and  to  greater  activity  of  the  feeding  reflexes  in  all. 
This  the  writer  has  observed  in  decerebrated  pigeons  kept  in  good 
condition  for  months  after  the  operation.  When  the  crop  becomes 
empty  this  bird  not  only  becomes  restless  and  keeps  walking  about 
incessantly,  but  picks  at  the  floor,  the  walls  of  the  cage,  or  the 
empty  air.  If  it  happens  to  pick  at  food  before  it,  there  is  no  indi- 
cation of  ^' recognition"  of  it  as  food.  Nor  does  it  open  its  beak  in 
going  through  the  motion  of  picking.  The  significant  fact  in  this 
connection  is  the  inducing  of  the  picking  reflex  by  the  hunger  state. 

In  the  newborn  everything  within  reach  goes  into  the  mouth 
to  be  rejected  or  swallowed  according  to  its  chemical  character  or 
physical  consistency.  It  would,  then,  seem  that  the  newborn  connects 
up  the  gastric  hunger  urge  with  the  processes  of  feeding  as  a  matter  of 
individual  experience  by  the  method  of  trial  and  error.  In  man  there 
is  conscious  direction  on  the  part  of  the  mother.  Conscious  direc- 
tion as  well  as  the  factor  of  imitation  probably  plays  a  role  in  newly 
hatched  chickens  '^ learning"  to  feed.  In  the  young  birds  that 
secure  their  food  by  thrusting  their  beak  and  head  down  the  throat 
of  the  mother,  maternal  direction  is  also  probably  the  initial  factor. 
The  hunger  sensation  induces  the  movements  of  sucking  in  the 
newborn  mammal,  while  in  the  newly  hatched  and  immature  bird 
it  causes  the  beak  to  be  set  wide  open.  Such  minor  differences 
are  obviously  a  matter  of  inherited  reflexes,  and  we  need  not  fall 
back  on  '^ instincts"  to  account  for  them. 

On  the  foregoing  hypothesis  the  connection  between  the  primary 
sensation  of  hunger  and  the  processes  of  feeding  is  a  matter  of 
individual  experience  by  the  method  of  ''trial  and  error."  The 
fundamental  factors  are  the  augmentation  of  all  reflexes  by  the 
gastric  hunger  state,  the  removal  of  the  hunger  pangs,  and  the 
production  of  the  opposite  sensation  of  satiety  by  sucking,  masti- 
cation, and  ingestion  of  food.  The  theory  demands  the  presence 
of  memory,  otherwise  each  feeding  act  or  feeding  period  becomes  a 
matter  of  trial  and  error. 


BIOLOGICAL  SIGNIFICANCE  OF  HUNGER  ii 

We  may  ask  whether  this  gap  between  the  pure  sensation  of 
hunger  and  the  ingestion  of  food  in  the  newborn  is  not  in  reality 
bridged  by  the  factor  of  appetite.  There  is  as  yet  great  uncertainty 
and  confusion  in  regard  to  the  elements  of  appetite,  and  the  relation 
of  appetite  to  hunger.  Many  physiologists  appear  to  accept  the 
view  that  appetite  and  hunger  involve  identical  mechanisms  and 
differ  only  in  degree  of  intensity.  That  is,  a  mild  state  of  hunger 
is  called  appetite,  and  a  strong  appetite  is  called  hunger.  There 
are  others  who  maintain  that  hunger  and  appetite  are  different, 
both  in  the  quality  of  the  sensation  and  in  the  mechanisms  involved 
in  the  genesis  of  the  sensation.  The  latter  view  appears  to  make  the 
nearest  approach  to  actual  conditions. 

Appetite,  as  we  know  it,  cannot  be  separated  from  our  memory 
of  past  experience  with  food,  that  is,  the  taste,  smell,  and  appear- 
ance of  food.  In  fact,  it  appears  to  be  essentially  pleasant  memory 
processes  of  these  past  experiences,  and  the  ''urge''  in  appetite 
may  be  only  a  special  case  of  the  general  desire  for  pleasure.  If 
this  is  the  case,  there  can  be  no  urge  for  food  in  the  absence  of  past 
experience  with  food  on  the  part  of  the  individual,  and  as  this  is 
lacking  in  the  newborn,  the  appetite  urge  must  also  be  wanting. 
Hence  it  is  not  the  factor  that  guides  the  newborn  individual  for 
the  first  time  to  abolish  the  pangs  of  hunger  by  ingestion  of  food. 
However,  it  is  conceivable  that  appetite  contains  an  elemental  urge 
for  food  as  an  inherited  mechanism  and  thus  not  dependent  on 
individual  experience,  and  that  when  the  individual  has  such 
experience  with  food,  memory  processes  of  this  experience  fuse 
with  or  overshadow  the  inheritance  factor,  so  that  the  two  cannot 
be  dissociated  in  consciousness.  This  inherited  appetite  urge,  if  it 
exists  at  all,  is  probably  essentially  a  positive  chemotropism  (smell, 
taste),  although  birds  hatched  sufficiently  mature  to  seek  their 
own  food  probably  select  or  seek  the  food  by  vision  rather  than 
by  smell. 

This  positive  chemotropism  for  food  may  in  the  newborn  of 
the  higher  animals  involve  an  element  of  pleasure.  It  is  clear  that 
such  an  inherited  positive  chemotropism  augmenting  the  motility 
and  guiding  the  movements,  plus  the  inherited  reflexes  of  taking 


12  CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

everything  within  reach  into  the  mouth,  will  lead  to  food  ingestion 
in  the  newborn,  even  in  the  absence  of  hunger.  But  if  the  latter  is 
present  the  food  ingestion  completes  the  experience  of  removal  of 
the  unpleasant  hunger  pangs  by  feeding.  Loeb  and  others  have 
referred  to  a  positive  chemotropism  as  a  factor  in  the  finding  and 
selection  of  food,  especially  in  the  lower  animals,  but  we  do  not  know 
whether  in  the  species  thus  controlled  a  state  of  hunger  means  an 
increased  excitability  and  augmented  motor  response  to  the  specific 
chemical  stimuli. 

It  would  thus  seem  that  the  first  ingestion  of  food  on  the  part 
of  the  newborn  or  newly  hatched  animal  that  feeds  unaided  by  the 
parents  can  be  accounted  for  by  either  of  the  theories  outlined 
above.  Given  the  hunger  pangs  with  its  effects  in  the  way  of 
increased  motility  and  reflex  excitability  and  the  inherited  reflexes 
of  putting  everything  within  reach  into  the  mouth,  plus  the  reflexes 
causing  rejection  of  injurious  or  "disagreeable"  material,  the  in- 
gestion of  food  becomes  only  a  question  of  it  being  within  reach, 
and  the  experience  of  removing  the  uncomfortable  pangs  of  hunger 
by  feeding  is  quickly  established.  On  the  other  hand,  given  an 
inherited  appetite  urge  or  positive  chemotropism,  so  that  certain 
olfactory  and  gustatory  stimuli  initiate  and  direct  the  reflexes 
and  possibly  produce  a  sensation  of  pleasure,  ingestion  of  food  is 
equally  inevitable. 

The  first  experience  of  feeding  once  gained,  the  individual  will 
feed  again  because  of  appetite,  that  is,  the  pleasure  in  the  tasting 
and  smelling  of  food,  and  the  pleasure  in  the  sensation  of  satiety, 
or  because  of  hunger  and  the  experience  that  feeding  removes  the 
hunger  pains. 

In  the  discussion  so  far  we  have  used  the  term  "food"  mostly 
in  the  restricted  sense  of  organic  food  substances.  In  a  wider 
sense  the  term  "food"  includes  all  materials  necessary  for  the 
continuance  of  the  life  of  the  animal.  The  sensations  induced  by 
the  lack  of  water  (thirst)  and  by  impairment  of  the  external  pro- 
cesses of  respiration  (dyspnea)  have  nothing  in  common  with  the 
sensation  of  hunger  (due  to  lack  of  pabulum  in  the  stomach), 
either  in  their  genesis  or  in  their  character,  except  that  all  three 


BIOLOGICAL  SIGNIFICANCE  OF  HUNGER  13 

sensation  complexes  are  more  or  less  uncomfortable  or  painful. 
But  we  may  speak  of  the  sensation  of  thirst  for  water  as  analogous 
to  the  sensation  of  hunger  for  food.  There  is,  however,  no  appetite 
for  water  analogous  to  the  appetite  for  food.  This  is  probably  due 
to  the  absence  of  taste  qualities  in  pure  water,  and  hence  to  absence 
of  memory  representations  of  taste.  In  the  case  of  beer  or  other 
artificially  flavored  drinks  that  may  be  taken  to  satisfy  thirst, 
taste  qualities  are  present,  and  persons  may  develop  an  appetite 
for  these  drinks  in  connection  with  as  well  as  in  the  absence  of  actual 
thirst,  just  as  we  may  have  appetite  for  certain  foods  with  or  without 
actual  hunger  sensation. 

V.     "salt  hunger" 

The  condition  referred  to  by  physiologists  as  "salt  hunger '^  is 
not  ordinarily  experienced  by  man,  except  as  a  preference  for  some 
degree  of  salt  flavor  in  the  diet.  But  this  cannot  be  the  factor  that 
makes  some  herbivorous  animals  travel  great  distances  to  "salt 
licks,"  because  the  salt  is  not  actually  mixed  with  their  food.  It 
is  well  known  that  depletion  of  the  sodium  chloride  content  of  the 
blood  and  the  tissues  below  a  certain  limit  leads  to  serious  disturb- 
ances in  organ  activity,  but  we  do  not  know  their  specific  effect  on 
consciousness.  Possibly  it  is  a  feeling  of  general  discomfort  and 
weakness,  rather  than  any  specific  quality  of  sensation  referred  to 
any  one  part  of  the  body,  although  marked  reduction  of  the  NaCl 
in  the  blood  leads  to  absence  of  the  hydrochloric  acid  in  the  gastric 
juice  and,  in  consequence,  digestive  disorders. 

The  experiments  of  Forster  on  dogs  and  pigeons,  and  those  of 
Lunin  on  mice  showed  that  animals  succumb  sooner  on  a  salt-free 
diet  than  if  they  are  given  no  food  at  all.  The  symptoms  developed 
by  these  animals  are:  weakness  and  cachexia,  nervous  hyper- 
excitabiHty,  tremors,  and  gastero-intestinal  disorders  (indigestion, 
vomiting,  refusal  of  food) .  It  is  still  an  open  question  whether  any 
animal,  man  included,  actually  needs  sodium  chloride  in  addition 
to  the  salts  present  in  all  natural  foodstuffs.  Smith,  the  veterinary 
physiologist,  maintains  that  "both  camivora  and  herbivora  obtain 
in  their  natural  diet  a  sufficiency  of  salts,  although  there  is  a 


14  CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

general  impression  that  the  wild  herbivora  long  for  sodium.  It  is 
quite  certain  that  under  conditions  of  domestication  horses  can  be 
kept  in  perfect  health  without  receiving  any  sodium  chloride  other 
than  that  contained  in  the  food,  and  the  amount  of  this  in  vegetable 
substances  is  very  small."  Nevertheless,  it  is  a  fact  that  herbivorous 
animals,  wild  as  well  as  domesticated,  ingest  sodium  chloride  when 
available,  while  this  is  not  done  by  the  out-and-out  carnivorous 
species.  History  seems  to  show  that  it  is  the  agricultural  races  or 
tribes  that  have  developed  the  need  or  at  least  the  greatest  desire 
for  salt.  According  to  Bunge,  among  the  races  living  exclusively 
or  mainly  on  animal  food,  salt  is  either  unknown,  unused,  or  actually 
disliked,  while  some  of  the  agricultural  tribes  in  Central  Africa 
cherish  salt  as  ardently  as  our  children  desire  sweets.  It  is  even 
believed  by  some  anthropologists  that  this  need  or  desire  for  salt 
or  animal  food  is  a  factor  in  cannibalism. 

Mungo  Park,  the  traveler,  describes  his  own  feelings  on  long- 
continued  salt  want  as  follows :  ^'  1  found  the  scarcity  of  salt  actually 
painful.  The  continued  subsistence  on  nothing  but  vegetable  food 
produced  finally  a  desire  for  salt  so  painful  that  it  can  hardly  be 
described."  We  are  not  familiar  with  any  prolonged  experiments 
with  salt-free  diets  on  man.  But  persons  on  ordinary  diets  who  have 
gone  for  a  long  time  without  sodium  chloride  complain  in  general  of 
lack  of  appetite  (owing  to  the  unpalatability  of  the  food),  and  of 
some  vague  or  general  bodily  distress — -a  condition  similar  to  that 
induced  by  monotonous  and  incomplete  diets. 

But  even  if  we  assume  th^t  the  herbivora  do  experience  a  ^^salt 
hunger"  in  the  sense  of  general  bodily  discomfort  and  weakness, 
or  special  distress  referred  to  the  digestive  tract,  how  do  the  animals 
know  that  eating  salt  will  reHeve  these  sensations,  and  how  do 
they  know  where  to  find  the  salt  ?  In  all  probability  it  is  a  matter 
of  individual  experiences  and  memory.  We  may  assume  that  a 
certain  amount  of  salt  flavor  is  pleasant  to  these  animals  as  a  matter 
of  inherited  reflexes  or  because  of  its  slight  stimulating  action. 
Hence  they  will  eat  or  lick  the  salt  wherever  found,  irrespective 
of  actual  need.  Now,  if  actual  salt  need  is  expressed  in  a  feeling 
of  general  bodily  distress,  and  salt  being  available,  the  animal  will 


BIOLOGICAL  SIGNIFICANCE  OF  HUNGER  15 

sooner  or  later  encounter  the  experience  that  eating  salt  eases  the 
distress.  As  long  as  the  calf  feeds  on  the  milk  of  its  mother,  no 
^additional  salts  are  required  in  its  diet.  But,  of  course,  the  calf 
follows  the  mother  to  the  ''salt  licks,"  and  through  imitation  or 
curiosity  learns  the  taste  of  salt  as  well  as  the  location  of  the  ''  licks," 
both  before  and  after  he  actually  experiences  salt  hunger.  Thus 
by  aid  of  the  parents  or  the  herd,  the  individual  experience  is 
established. 


CHAPTER  II 

HISTORICAL 

I.      THEORIES   OF  HUNGER  AND   APPETITE 

The  theories  so  far  advanced  to  explain  the  genesis  of  hunger 
and  appetite  fall  into  three  main  groups,  namely,  those  involving 
the  stimulation  of  sensory  nerves  mainly  in  the  digestive  tract — a 
peripheral  origin;  those  involving  a  direct  stimulation  of  a  hypo- 
thetical ''hunger  center"  in  the  brain  by  the  blood,  or  by  some 
changes  in  the  metabolism  in  the  center  itself — a  central  origin; 
and  lastly  those  involving  a  combination  of  both  central  and  general 
peripheral  factors  of  hunger — a  general  sensation. 

Theories  of  peripheral  origin  of  hunger. — The  theories  of  a  purely 
peripheral  origin  of  hunger  may  in  turn  be  grouped  under  two 
heads,  viz.,  (i)  The  stimulation  of  a  strictly  local  group  of  sensory 
nerves  (mainly  in  the  stomach),  and  (2)  the  stimulation  of  all 
afferent  nerves  by  some  change  in  the  tissues  or  in  the  blood.  We 
shall  first  outline  the  theories  that  account  for  the  hunger  sensation 
by  the  stimulation  of  sensory  nerves  in  the  digestive  tract.  There 
are,  to  the  author's  knowledge,  at  least  six  such  theories,  namely: 
(i)  Hunger  is  due  to  mechanical  stimulation  of  sensory  nerves  in 
the  gastric  mucosa  by  mechanical  rubbing  or  pressure  from  con- 
traction of  the  stomach.  (2)  Hunger  is  due  to  chemical  stimulation 
of  sensory  nerves  in  the  gastric  mucosa  (the  acid  of  the  gastric 
juice,  etc.).  (3)  Hunger  is  due  to  the  stimulation  of  sensory  nerves 
in  the  gastric  mucosa  by  a  state  of  turgescence  of  the  gastric  glands. 
(4)  Hunger  is  due  to  the  stimulation  of  sensory  nerves  in  the  gastric 
mucosa  by  some  change  in  the  blood  due  to  starvation.  (5)  Hunger 
is  due  to  stimulation  of  sensory  nerves  in  the  stomach  by  the  atony 
and  absence  of  contractions  of  the  empty  stomach.  (6)  Hunger  is 
due  to  the  stimulation  of  sensory  nerves  in  the  wall  of  the  stomach 
(muscularis  or  submucosa)  especially  in  the  fundus  and  cardiac 
regions,  by  contraction  of  the  empty  or  partly  empty  stomach. 

16 


HISTORICAL  17 

Sternberg's  literary  essays  on  hunger  and  appetite  contain 
numerous  references  to  the  conceptions  of  hunger  and  appetite 
held  by  the  ancient  and  mediaeval  poets  and  philosophers;  but 
there  appears  to  be  little  or  nothing  specific  concerning  the  hunger 
and  appetite  mechanisms  in  the  writings  of  either  Hippocrates  or 
Galen,  although  the  popular  view  that  prolonged  starvation  or 
hunger  is  extremely  painful  dates  back  at  least  to  the  time  of  Homer. 
Hippocrates  does  remark  in  one  of  his  famous  Aphorisms,  that 
''strong  wine  cures  hunger,"  but  the  modus  of  this  cure  did  not 
appear  to  interest  him.  The  theory  that  the  sensation  of  hunger 
is  due  to  mechanical  stimulation  of  sensory  nerves  in  the  gastric 
mucosa  goes  back  at  least  one  hundred  and  fifty  years  to  the  great 
physiologist  Haller.  On  the  subject  of  the  immediate  cause  of 
hunger,  Haller  wrote : 

Hunger  is  initiated  and  intensified  by  bodily  vigor,  as  in  the  athlete  Milo, 
in  lions,  and  in  all  animals  possessing  great  strength  by  a  peculiar  strength  of 
the  stomach  and  by  physical  labor  of  all  kinds,  especially  at  low  temperature, 
since  hunger  is  intensified  in  cold  climates. 

Hunger  is  increased  by  the  presence  of  intestinal  worms,  as  they  consume 
part  of  the  nutrient  juice.  It  is  also  augmented  by  the  patency  of  the  pylorus, 
a  condition  normally  present  in  voracious  animals,  and  resulting  in  an  almost 
continuously  empty  stomach.  The  sensation  of  hunger  is  sometimes  even  ex- 
cited by  certain  acids,  such  as  cream  of  tartar,  lemon  juice,  and  similar  sub- 
stances while  regurgitation  by  putrefying  intestinal  contents  into  the  stomach 
depresses  and  prevents  hunger.  The  numerous  kinds  of  fruits  especially  enjoyed 
by  the  people  of  the  Orient  are  generally  acid. 

A  greater  degree  of  excitabiUty  of  the  (gastric)  nerves  also  induces  greater 
hunger. 

Finally  there  are  imperfectly  understood  conditions  characterized  by  an 
inordinate  augmentation  of  hunger,  excessive  eating,  and  ingestion  of  unusual 
or  indigestible  substances. 

Among  animals,  those  having  the  shortest  span  of  life,  such  as  the 
insects,  are  the  most  voracious  feeders.  The  caterpillar  eats  and  defecates 
continuously. 

Thus,  we  see,  on  the  basis  of  the  phenomena  of  hunger  in  the  entire  animal 
kingdom,  the  immediate  cause  of  the  sensation  of  hunger  is  the  grinding  or 
rubbing  (tritus)  of  the  delicate  and  vilous  folds  of  the  gastric  mucosa  against 
each  other,  through  a  motion  or  contraction  inherent  in  the  stomach,  aided 
by  the  diaphragm  and  the  abdominal  muscles.     These  I  consider  as  facts 


1 8  CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

already  demonstrated.  A  famous  man^  has  suggested  that  the  gastric  nerves 
thus  irritated  are  restored  by  the  congestion  of  blood  in  the  mucus  folds,  as 
occurs  in  all  cases  of  irritation. 

We  can  show,  moreover,  that  the  empty  stomach  is  contracted  so  that 
no  lumen  exists.    In  a  hungry  man  the  stomach  is  contracted  (pinched). 

From  our  knowledge  of  the  intolerable  sensation  produced  by  rubbing 
the  exposed  nerves  in  a  region  where  the  skin  has  been  lacerated  or  broken, 
we  are  permitted  to  estimate  how  acute  must  be  the  sensation  caused  by  this 
friction  or  stimulation  of  exposed  nerves  on  the  gastric  mucosa,  as  in  prolonged 
hunger.    I  would  not  care  to  face  such  a  sinister  exitus. 

These  considerations  make  it  clear  why  a  long-continued  fast  causes  only 
mild  hunger  in  animals  like  the  snake,  in  whose  stomach  there  is  scarcely  any 
grinding  action,  as  it  is  not  sufficiently  muscular;  besides  the  strength  of  the 
abdominal  muscles  and  the  diaphragm  is  almost  nil.  They  also  explain  why 
chickens  die  sooner  from  starvation  than  do  dogs,  cats,  and  carnivorous  animals 
in  general.  Indeed,  the  grinding  action  of  the  stomach  in  the  gallinaceous 
birds  is  stronger  than  in  the  quadrupeds.  In  some  insects  with  feeble  peristalsis 
of  the  alimentary  tract  there  is  no  hunger  in  winter,  but  in  the  summer  the 
hunger  is  greater  the  greater  the  heat. 

So  far  Haller.  It  is  probable  that  Haller  confuses  hunger  with 
appetite  when  he  speaks  of  acids  or  bitter  fruits  augmenting  hun- 
ger, although  if  the  sensory  nerves  of  the  hunger  sense  are  distrib- 
uted in  the  gastric  mucosa,  the  possibility  of  these  nerves  being 
stimulated  by  certain  chemicals  in  the  stomach  cavity  cannot  be 
excluded.  The  central  facts  in  Haller 's  conception  are  the  tonicity 
and  contractions  of  the  empty  stomach  stimulating  the  hunger 
nerves  in  the  mucosa  by  pressure  and  rubbing. 

Erasmus  Darwin  thought  that  the  hunger  pain  is  due  to  the 
atonicity  and  absence  of  contractions  in  the  empty  stomach.  The 
view  that  the  empty  stomach  of  normal  individuals  is  atonic  and 
quiescent  has  persisted  in  physiological  and  medical  literature  to 
this  day,  despite  both  early  and  recent  evidence  to  the  contrary. 

Johannes  Miiller,  one  of  the  fathers  of  modern  biology,  states 
that  hunger  is  a  kind  of  negative  sensation — or  simply  due  to  the 
absence  of  the  positive  sensation  generated  in  the  stomach  during 
digestion.  If  this  is  the  case,  an  individual  should  always  feel 
hunger  after  excision  of  the  stomach  or  after  section  of  both  vagi 

^  The  physiologist  Senac. 


HISTORICAL  19 

nerves.  Miiller  notes,  however,  that  the  stomach  of  animals  after 
prolonged  fasting  or  after  death  from  starvation  appears  very  much 
contracted. 

Weber  considered  it  probable  that  '^sudden  and  strong  contrac- 
tion of  the  empty  stomach,  completely  obliterating  the  gastric 
cavity,  gives  rise  to  a  part  of  the  sensation  we  call  hunger."  As 
analogies  to  the  hunger  pangs  he  refers  to  the  labor  pains  (uterine 
contraction),  the  pangs  from  the  large  intestine  in  tenesmus,  and 
from  the  small  intestine  in  cases  of  cohc.  Weber  does  not  explain 
how  the  gastric  contractions  stimulate  the  hunger  nerves.  This 
general  view  that  the  hunger  is  caused  by  contractions  of  the  empty 
stomach  has  been  accepted  by  a  number  of  physiologists  and  clini- 
cians (Vierordt,  Hertz,  Knapp,  and  Sternberg),  and  finally  demon- 
strated by  Cannon  and  Washburn,  and  Carlson.  Voit,  Albu, 
Stiller,  Nicolai,  and  others  assume  a  gastric  genesis  of  hunger 
without  going  into  the  question  of  how  the  stimulation  is  brought 
about.  Sternberg  has  designated  hunger  as  ''Pruritus  stomachi," 
or  a  tickling  sensation,  similar  to  that  evoked  from  mechanical 
stimulation  of  certain  cutaneous  areas.  He  also  suggests  that 
appetite  is  in  some  way  correlated  with  the  peristalsis  of  the  esoph- 
agus and  stomach  and  that  absence  of  appetite  or  nausea  is 
similarly  associated  with  antiperistalsis.  Sternberg's  papers  on 
the  subject  of  hunger  and  appetite  contain  no  original  observations, 
and  one  meets  with  a  number  of  contradictions  and  far-fetched 
analogies  that  prove  nothing.  Thus  Sternberg  says  that  ''the 
empty  stomach  is  anatomically  an  atonic  folded  tube."  Now,  an 
atonic  stomach  cannot  give  rise  to  hunger  by  contraction  or  peri- 
stalsis, for  the  simple  reason  that  these  are  not  present,  except  when 
there  is  a  certain  degree  of  tonus. 

The  turgescence  theory  of  hunger  as  formulated  by  Beaumont  is 
untenable,  for  the  reason  that  there  is  no  actual  accumulation  of 
gastric  juice  in  the  crypts  of  the  glands  in  the  empty  stomach  to 
stimulate  the  gastric  nerves  by  distension.  Moreover,  there  may 
be  a  continuous  secretion  of  gastric  juice  during  a  hunger  period. 
Yet  the  theory  is  accepted,  at  least  in  part,  by  some  recent  workers 
(Luciani,  Valenti). 


20  CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

The  theory  that  the  sensation  of  hunger  is  a  mere  negative 
phenomenon,  or  the  absence  of  the  positive  sensation  accompanying 
the  filled  stomach,  has  not  received  much  attention.  If  we  consult 
our  own  experience,  the  hunger  urge  appears  to  be  a  sensation  as 
positive  as  pain.  We  also  know  that  the  mere  emptiness  of  the 
stomach  does  not  initiate  the  sensation. 

The  view  that  hunger  is  due  to  the  chemical  stimulation  of 
nerves  in  the  gastric  mucosa  appears  also  to  lead  back  at  least  to 
Haller.  Soemmering  ascribes  the  hunger  pains  of  fasting  to  the 
action  of  gastric  juice  on  the  mucosa  nerves.  Bostock  accepts  the 
theory  and  credits  it  to  ^'the  chemical  physiologists''  (the  itra- 
chemical  school?).  Cannon  thinks  it  is  based  mainly  on  clinical 
evidence  in  cases  of  so-called  gastric  hyperacidity  and  hypersecre- 
tion. Pavlov  appears  to  accept  it,  when  he  cites  his  own  experience 
of  hunger  being  initiated  by  a  small  quantity  of  wine  passed  into 
the  stomach.  It  is  well  established,  ho\vever,  that  we  may  feel 
hunger  when  the  stomach  is  completely  empty  of  gastric  juice  and 
other  substances  that  may  be  capable  of  stimulating  the  nerves 
in  the  mucosa.  Some  mucus  is  always  present  in  the  stomach,  but 
there  is  no  evidence  that  this  can  act  as  chemical  stimulus.  It  is 
also  known  that  in  cases  of  complete  absence  of  hydrochloric  acid 
in  the  gastric  juice  (achylia  gastrica)  hunger  may  be  present. 

Theories  of  the  central  origin  of  hunger. — Magendie  thought  that 
hunger  is  strictly  of  central  origin,  not  even  directly  due  to  depletion 
of  the  blood  or  the  tissues,  since  both  the  gastric  sensation  and  the 
general  feeling  of  weakness  may  pass  away  without  the  individual 
partaking  of  food.  He  denied  tonic  or  periodic  contractions  of  the 
empty  stomach,  at  least  during  the  first  3  to  5  days  of  fasting,  and 
quotes  only  to  reject  mechanical  stimulation  of  the  stomach  walls, 
traction  on  the  liver  by  the  diaphragm,  fatigue  (atony)  of  the 
gastric  musculature,  bile  and  gastric  juices  in  the  stomach  as  causes 
of  hunger;  but  he  does  not  deny  that  sensory  impulses  for  the  organs 
in  general  may  be  contributing  factors.  Tidemann,  Schiff,  Ewald, 
Wundt,  Milne  Edwards,  and  others  adhere  in  the  main  to  this 
theory  but  assume  that  the  hunger  center  is  stimulated  by  a  starva- 
tion state  of  the  blood.     Many  authors  have  pointed  out  the 


HISTORICAL  21 

analogous  condition  in  the  case  of  the  respiratory  center  being 
stimulated  by  the  venous  condition  of  the  blood. 

The  main  objection  urged  against  this  theory  is  its  failure  to 
explain,  (i)  the  reference  of  the  hunger  sensation  to  the  stomach; 
(2)  the  fact  that  hunger  may  be  temporarily  aboHshed  by  the 
eating  of  indigestible  materials,,  and  (3)  the  periodicity  of  the 
hunger  sensation. 

The  main  arguments  urged  by  exponents  of  the  central  theories 
against  the  gastric  origin  of  hunger  are:  (i)  Man  and  animals  will 
eat  after  excision  of  the  stomach,  or  after  section  of  the  sensory 
nerves  to  the  stomach.  (2)  Hunger  may  be  present  even  when  the 
stomach  is  partly  filled  with  food.  (3)  Hunger  may  be  appeased 
by  feeding  per  rectum  as  well  as  by  intravenous  injections  of  food- 
stuffs. 

Hunger  a  general  sensation. — ^As  formulated  by  Bardier,  this 
theory  assumes  that  the  hunger  center  in  the  brain  is  stimulated 
directly  by  some  change  in  the  blood,  and  indirectly  by  afferent 
nervous  impulses  from  all  organs  of  the  body,  the  stimulation  of 
these  afferent  nerves  being  also  due  to  some  change  in  the  blood 
induced  by  the  state  of  hunger.  With  certain  minor  modifications 
and  additions,  this  view  is  accepted  by  Longet,  Beaunis,  Roux, 
M.  Foster,  J.  L.  Miiller,  Schlessinger,  and  others.  According  to 
Roux  the  gastric  moiety  of  the  peripheral  part  of  the  hunger  sense 
constitutes  appetite,  that  is,  appetite  is  due  to  the  stimulation  of 
sensory  nerves  in  the  stomach  by  the  starvation  changes  in  the 
blood.  Miiller,  writing  in  19 15,  cannot  very  well  deny  the  gastric 
hunger  contractions,  but  he  assumes  that  these  contractions  are 
caused  through  motor  impulses  in  the  vagi  nerves  by  stimulation  of 
the  hunger  center  in  the  brain  by  the  blood,  although  this  possibiHty 
was  disproved  in  19 13  by  Carlson.  That  the  stimulation,  central 
and  peripheral,  is  brought  about  by  some  changes  of  the  blood 
in  starvation,  is  the  main  element  in  the  theory.  The  analogy  of 
this  mechanism  to  that  of  the  genesis  of  thirst  from  the  osmotic 
concentration  of  the  blood  has  been  frequently  pointed  out  in 
support  of  the  theory.  DuBois-Reymond  (quoted  from  Nicolai) 
postulated  a  vagus  hunger  (gastric  origin)  and  a  tissue  hunger  (the 


22  CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

feeling  of  weakness) .  Turro  advances  a ' '  trophic  reflex  mechanism ' ' 
of  hunger.  Lack  of  nutrient  material  stimulates  nerve-endings  in 
all  organs.  The  impulses  pass  to  a  hypothetical  trophic  center  in 
the  basal  gangHa  of  the  brain,  and  these  lower  centers,  in  turn, 
afifect  consciousness.  He  intimates  that  this  ''trophic  hunger 
mechanism"  is  so  perfectly  adjusted  by  inheritance  that  the  animal 
on  seeing  food  knows  instinctively,  as  it  were,  just  how  much 
salt,  water,  fat,  starch,  and  protein  to  ingest. 

The  objections  raised  by  various  authors  against  this  theory 
are:  (i)  Hunger  may  set  in  before  intestinal  absorption  is  com- 
pleted, and  therefore  before  there  can  be  any  starvation  change 
in  the  blood.  (2)  There  are  not  very  marked  chemical  changes  in 
the  blood  even  in  prolonged  starvation.  (3)  Hunger  is  abolished 
temporarily  by  the  eating  of  indigestible  matter,  and  by  taking 
food  hunger  ceases  before  any  of  the  food  is  digested  and  absorbed. 
(4)  Hunger  is  usually  more  or  less  periodic  with  sudden  onsets  and 
endings,  while  changes  in  the  composition  of  the  blood  from  starva- 
tion are  more  Hkely  to  be  gradual  and  continuous.  (5)  In  very 
prolonged  starvation  hunger  does  not,  at  least  in  man,  increase  in 
intensity  with  the  supposed  depletion  of  the  blood,  and  in  fevers 
hunger  may  be  absent  despite  prolonged  starvation  with  increased 
metabolism. 

That  the  sensation  of  hunger  is  not  an  evidence  of  the  immediate 
need  of  food  because  of  starvation  changes  in  the  blood  was  pointed 
out  by  Voit  in  the  following  way.  The  people  of  Ireland,  used  to 
voluminous  rations  of  potatoes,  complain  of  starvation  and  hunger 
when  given  even  greater  food  values,  but  in  smaller  bulk.  The 
same  is  true  of  the  bread-eating  peasants  of  Bavaria  when  put  on 
a  diet  of  meat. 

II.      HISTORICAL  STEPS   IN  THE  EXPERIMENTAL  INVESTIGATION 
OF  THE  HUNGER  MECHANISM 

The  earliest  experimental  work  on  the  hunger  mechanism  was 
directed  to  the  nerves  of  the  stomach,  namely,  the  vagi  and  the 
splanchnics.  Sedillot,  Bernard,  Bidder  and  Schmidt,  Eudge, 
Brunner  and  Hensen,  Longet,  Schiff,  Ewald,  Sherrington,  Ducceschi, 
and  others  observed  that  animals  will  continue  to  exhibit  desire  for 


HISTORICAL  23 

food  and  to  eat  after  section  of  the  vagi,  the  splanchnic,  and  even 
the  taste  nerves.  Some  of  these  men  concluded  that  hunger  does 
not  rise  from  stimulation  of  sensory  nerves  in  the  stomach,  on  the 
assumption  that  an  animal  will  eat  from  hunger  only.  Ludwig, 
Cannon,  and  others  have  questioned  the  validity  of  this  assumption. 
It  is  certain  that  man  at  any  rate  may  eat  from  appetite  alone  in 
the  absence  of  hunger,  as  in  the  case  of  eating  sweets  or  dessert  at  the 
conclusion  of  a  dinner.  Man  may  even  eat  from  habit  or  a  sense 
of  duty,  in  the  absence  both  of  hunger  and  appetite,  but  it  is  not 
likely  that  this  applies  in  a  like  measure  to  animals  below  man. 
Assuming,  for  the  present,  that  appetite  is  in  part  a  memory 
process,  and  hence  a  central  nervous  system  phenomenon  essen- 
tially, it  is  clear  that  section  of  the  vagi  would  not  affect  it;  hence 
the  fact  that  an  animal  eats  after  section  of  the  vagi  tells  us  nothing 
as  to  presence  or  absence  of  hunger.  Luciani  states  that  fasting 
dogs  refuse  to  eat  for  some  time  after  double  vagotomy.  Valenti 
cocainized  the  vagi  and  the  gastric  mucosa  in  fasting  dogs  and 
reports  that  the  animals  refused  food  for  some  hours.  These 
results  of  Valenti  on  dogs  are  called  in  question  by  L.  R.  Miiller 
on  the  basis  of  analogous  experiments  on  man.  Muller  states 
that  cocaine  by  mouth  .has  little  or  no  influence  on  the  gastric 
hunger  pangs,  but  it  abolishes  the  feeling  of  weakness  whether 
the  drug  is  taken  by  mouth  or  injected  subcutaneously.  He 
concludes  that  this  is  a  central  action  of  the  cocaine  after  absorp- 
tion into  the  blood. 

The  advance  of  modern  surgery  has  made  possible  the  nearly 
complete  removal  of  the  stomach  in  man  and  experimental  animals. 
It  is  reported  that  such  persons  continue  to  experience  hunger 
after  the  operation,  but  it  is  not  clear  that  patients  and  observers 
differentiated  between  hunger  and  appetite.  A  dog  minus  the 
greater  part  of  the  stomach  will  eat,  but  we  have  already  pointed 
out  that  this  is  no  absolute  criterion  of  hunger.  It  should  be  noted 
here  that  complete  excision  of  the  stomach  is  impossible,  or  at  least 
has  not  yet  been  accomplished.  There  always  remains  a  consider- 
able portion  of  the  stomach  around  the  cardia  where  the  union 
with  the  duodenum  is  made,  and  in  healthy  individuals  at  any  rate 


24  CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

this  gastric  remnant  gradually  hypertrophies  and  dilates  to  form  a 
considerable  stomach  pouch,  sufficient  in  all  likelihood  to  give  rise 
to  hunger  pangs,  especially  as  these  are  primarily  originated  in  the 
cardiac  end  of  the  stomach.  The  recent  observations  of  Perthes 
are  of  importance  in  this  connection.  In  cases  of  resection  of  the 
stomach  for  gastric  ulcers,  Perthes  states,  when  the  location  of 
the  ulcer  is  such  that  the  operation  removes  most  of  the  greater 
curvature  of  the  stomach  body,  after  recovery  X-ray  observations 
show  the  pylorus  permanently  open,  the  diminutive  stomach  ex- 
hibits hypermotility,  and  the  food  passes  out  of  the  stomach 
practically  at  once  and  without  any  gastric  digestion.  All  these 
patients  complained  of  bulimia  or  excessive  hunger  pangs.  In 
some  cases  the  hunger  pangs  were  strong  enough  to  wake  the 
persons  up  from  sleep.  In  order  to  be  comfortable  they  had  to  eat 
every  two  hours.  This  excessive  hunger  did  not  develop  in  patients 
with  stomach  so  resected  that  the  main  body  or  reservoir  of  the 
stomach  was  left  intact. 

The  observations  of  Busch,  in  1862,  on  a  woman  with  a  duodenal 
fistula,  have  been  extensively  quoted  in  subsequent  discussions  on 
the  hunger  mechanism.  The  patient  was  a  woman  thirty-one  years 
old.  She  was  greatly  emaciated  owing  to  loss  of  chyme  from  the 
fistula,  weighing  only  68  lbs.  when  she  came  under  Dr.  Busch's 
care.  She  had  inordinate  hungei:  (bulimia)  and. felt  the  hunger 
even  when  her  stomach  was  practically  filled  with  food.  But 
taking  food  into  the  stomach  relieved  that  part  of  the  hunger  which 
may  be  described  as  a  painful  or  gnawing  sensation  in  the  stomach. 
Hunger  was  also  relieved  in  part  by  the  introduction  of  chyme  into 
the  duodenum.  The  woman  was  so  emaciated  that  the  stomach 
and  intestinal  movements  could  be  seen  in  detail  through  the 
abdominal  wall,  and  Busch  observed  periods  of  active  peristalsis 
alternating  with  periods  of  rest  in  the  case  of  the  empty  intestines. 
He  could  not  make  out  any  regularity  in  the  recurrence  of  these 
activity  periods.  Busch  concludes:  The  sensation  of  hunger  is 
made  up  of  two  elements.  The  first  is  a  condition  of  the  central 
nervous  system,  in  consequence  of  actual  tissue  starvation;  the 
second  is  due  to  stimulation  of  nerves  in   the   alimentary   tract. 


HISTORICAL  25 

In  extreme  starvation  the  central  element  persists  even  when  the 
alimentary  tract  is  filled  with  food. 

Nicolai,  in  1892,  made  some  observations  on  normal  persons, 
and  on  persons  with  various  gastero-intestinal  disorders.  He  found 
that  the  mere  act  of  swallowing  or  passing  the  stomach  tube 
abolishes  hunger  temporarily.  Passing  water,  salt  solution,  or 
indigestible  material  through  the  tube  into  the  stomach  also  allays 
hunger  for  varying  periods.  These  observations  are  now  readily 
explained  by  the  inhibitory  reflexes  from  the  mouth  and  the  gastric 
mucosa  to  the  gastric  musculature.  Nicolai  concludes  that  ^'the 
sensation  of  hunger  involves  sensory  impulses  not  only  from  the 
stomach,  but  also  from  the  esophagus,  and  the  pharynx,"  and  that 
appetite  and  hunger  are  fundamentally  different  sensations,  either 
of  which  may  be  experienced  without  the  other. 

Schlessinger,  in  1893,  fed  normal  patients  and  persons  exclu- 
sively per  rectum  for  periods  varying  from  i  to  20  days.  He  reports 
that  rectal  feeding  does  not  abolish  completely  the  sensation  of 
hunger,  even  when  this  feeding  leads  to  an  increased  body  weight. 
At  the  most  there  is  a  decrease  in  the  hunger  sensation  for  a  short 
time  after  each  rectal  feeding.  On  the  basis  of  more  recent  work, 
this  is  probably  due  to  inhibitory  reflexes  from  the  rectum  and 
large  intestine  to  the  gastric  musculature.  Schlessinger  reports 
further  that  local  anesthesia  of  the  gastric  mucosa  (pieces  of  ice, 
chloroform,  cocaine  in  the  stomach)  causes  only  a  slight  or  temporary 
abolition  of  hunger.  But  if  the  persons  had  been  previously  fed 
per  rectum,  local  anesthesia  of  the  gastric  mucosa  led  to  complete 
disappearance  of  hunger.  He  therefore  concludes  that  hunger  has 
a  double  origin :  (i)  peripheral  or  gastric,  and  (2)  central  stimulation 
of  a  hunger  center  by  starvation  blood. 

Boring,  a  psychologist,  has  recently  reported  a  subjective 
analysis  of  the  character  of  the  hunger  sensation,  based  on  the 
experiences  of  a  great  number  of  persons.  He  concludes  that  hun- 
ger is  a  complex  of  pressure  and  pain. 

Upon  a  background  of  dull  pressure,  which  is  sometimes  recognized  defi- 
nitely as  kenisthesis  or  the  equivalent  muscular  pressure,  there  is  set  a  dull 
ache  or  gnawing  pain  which  characterizes  the  hunger.    Both  pain  and  pressure 


26  CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

are  referred  to  the  region  of  the  stomach.  The  pain  is  noted  as  fluctuating,  as 
rhythmical,  as  unstable.  Three  of  the  observers  described  in  addition  a  com- 
plex kinesthesis  in  the  throat,  and  oral  sensations  arising  from  the  free  flow  of 
saliva,  a  complex  which  meant  for  them  a  desire  for  food  or  appetite.  Here 
we  have  the  true  sensory  basis  for  appetite. 

According  to  Boring  hunger  is  a  twofold  experience.  It  is  pres- 
sure in  its  weak  form,  pain  and  pressure  when  intense.  This  recog- 
nition of  a  pressure  or  kinesthetic  element  in  the  hunger  pains  is 
important,  and  has  been  made  by  previous  observers. 

As  the  reader  will  recall,  the  great  physiologist,  Haller,  stated 
that  the  ''stomach  of  a  starving  man  is  contracted,"  and  the 
sensation  of  hunger  is  due  to  the  rubbing  of  the  folded  mucosa  by 
this  contraction.  But  during  the  one  hundred  and  fifty  years  since 
Haller 's  Elementa  appeared  the  contracted  condition  of  the  stomach 
in  starvation  has  been  questioned,  denied,  or  forgotten.  Schiff 
wrote  (in  1867):  ''The  movements  of  the  empty  stomach  are 
rare,  and  much  less  energetic  than  during  digestion,"  and  as 
late  as  the  year  19 10  Valenti  stated  that  contractions  in  the  empty 
stomach  are  rare  and  feeble.  The  authors  who  followed  Haller 
and  Weber  in  accepting  the  gastric  contraction  theory  of  hunger 
did  so  essentially  without  experimental  evidence.  We  take  it  that 
all  men  have  observed  or  experienced  rumbling  noises  (borborygmi) 
in  the  abdomen  during  the  period  when  they  feel  strong  hunger. 
The  noises  are  due  to  movements  of  gas  by  contraction  of  some 
part  of  the  alimentary  tract  below  the  esophagus.  When  the 
noises  are  accompanied  by  the  expulsion  of  gas  or  air  from  the 
stomach  into  the  esophagus  the  contractions  are  evidently  in 
the  stomach  itself,  since  this  occurs  in  the  absence  of  contractions 
of  the  abdominal  muscles  and  the  diaphragm.  However,  in  certain 
"nervous"  persons  the  borborygmi  may  be  very  pronounced  with- 
out being  associated  with  hunger,  and  it  is  obvious  that  these 
noises  may  be  produced  in  the  large  as  well  as  the  small  intestines. 
Hertz  thinks  that  these  noises  arise  exclusively  from  contrac- 
tions of  the  small  intestines.  Nevertheless,  the  fact  that  the 
borborygmi  are  so  frequently  associated  with  hunger  does  not 
appear  to   have   been   fully  appreciated  in  connection  with  the 


HISTORICAL  27 

genesis  of  the  hunger  sensation,  until  Hertz  and  Cannon  recently 
called  attention  to  it. 

The  view  that  the  empty  stomach  is  atonic  and  quiescent  is 
the  more  readily  accepted,  as  contractions  would  seem  to  have  no 
useful  purpose,  except  when  there  is  food  in  the  stomach.  Now 
and  then  later  observers  (Bettmann,  Wolff,  His)  did  record  that 
the  stomachs  of  starving  men  and  other  animals  are  tonically 
contracted,  but  the  first  important  study  and  conclusive  demon- 
stration of  the  motor  phenomena  of  the  stomach  in  starvation  we 
owe  to  Boldyreff  in  1905,  although  this  investigator  did  not  connect 
the  gastric  contractions  with  the  genesis  of  the  hunger  sensation. 
Working  on  dogs  with  inflated  balloons  in  the  stomach,  Boldyreff 
found  that  the  stomach  of  starving  dogs  exhibits  alternate  periods 
of  strong  contractions  and  absolute  quiescence,  at  least  during  the 
first  3  to  4  days  of  starvation.  The  contraction  periods  last  20  to 
30  minutes,  the  quiescent  periods  for  i  J  to  2f  hours.  The  period  of 
activity  is  made  up  of  10  to  20  contractions  separated  by  intervals 
of  I  to  1 1  minutes,  beginning  with  feeble  contractions  and  gradually 
reaching  their  maximum  strength  at  the  end  of  the  period.  During 
these  periods  of  gastric  motor  activity  there  were  also  contractions 
in  the  intestines.  Boldyreff  states  that  the  contractions  of  the 
empty  stomach  are  stronger  than  the  gastric  peristalsis  during 
digestion.  There  were  no  contractions  in  the  empty  stomach  dur- 
ing the  periods  when  the  gland  secreted  gastric  juice  copiously. 
Hertz  (191 1)  gave  a  different  interpretation  to  these  contractions, 
namely,  that  they  give  rise  to  the  hunger  sensation. 

These  are  fundamental  and  important  facts.  Boldyreff  did  not 
think  that  these  gastric  contractions  gave  rise  to  the  sensation  of 
hunger,  mainly  because  they  diminished  in  strength  with  the  length 
of  starvation.  He  suggests  the  possibihty  that  the  state  of  hunger 
in  the  brain  initiates  the  gastric  and  intestinal  contractions  via  the 
motor  nerve  fibers  in  the  vagi.  It  seems  hardly  necessary  to  point 
out  that  the  genetic  relations  of  the  contractions  of  the  empty 
stomach  to  the  hunger  sensations  cannot, be  estabhshed  with  cer- 
tainty on  experimental  animals  below  man,  because  of  the  difficulty 
in  determining  the  kind  of  sensation  experienced  by  the  animal.* 


28  CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

In  1 910  Hudek  and  Stigler  reported  that  the  stomach  empties 
faster  when  the  food  is  eaten  with  hunger  than  when  eaten  without 
hunger.  Cannon  cites  this  fact  as  evidence  that  the  stomach  is  in 
greater  tonus  in  the  hunger  state.  It  is  obvious,  however,  that  an 
equally  important  factor  is  the  greater  rate  of  digestion  owing  to 
the  appetite  gastric  juice.  The  difference  in  the  time  of  emptying 
of  the  stomach  observed  by  Hudek  and  Stigler  may  be  due  to  this 
factor  alone. 

In  191 1  Cannon  and  Washburn  by  experiments  on  man  (Wash- 
burn) proved  that  the  periods  of  contractions  in  the  empty  stomach 
are  synchronous  with  the  periods  of  hunger  sensation,  and  that  each 
separate  contraction  is  synchronous  with  a  hunger  pang.  In  their 
experiments  a  small  balloon  was  swallowed  into  the  stomach  and 
the  stomach  contractions  were  recorded  graphically  parallel  with  a 
signal  showing  when  the  subject  felt  the  hunger.  These  observers 
also  obtained  evidence  of  contractions  in  the  lower  third  of  the 
esophagus,  synchronous  with  the  gastric  contractions,  and  con- 
clude that  the  esophagus  plays  a  part  in  the  genesis  of  hunger. 
While  noting  that  the  hunger  sensation  tends  to  lag  behind  the 
gastric  contraction  both  at  its  beginning  and  its  cessation,  their 
experiments,  nevertheless,  do  not  prove  that  the  gastric  and 
esophagus  contractions  cause  the  sensation  of  hunger  by  stimu- 
lation of  sensory  nerves,  but  they  assume  this  to  be  the  mechanism. 
Nor  do  they  indicate,  on  this  assumption,  whether  the  nerves  stimu- 
lated are  those  in  the  gastric  mucosa,  or  in  the  muscular  wall  of 
the  stomach.  This  demonstration  of  the  synchrony  of  the  gastric 
contractions  and  the  subjective  feeling  of  hunger  is  an  important 
step,  but  it  does  not  inform  us  which  is  the  cause  and  which  the 
effect.  In  other  words,  adherents  of  central  or  hunger-center 
theory  may  still  maintain  that  the  gastric  contractions  are  initiated 
by  motor  discharges  via  the  vagi  nerves  under  the  influence  of  a 
periodic  activity  in  the  lounger  center  in  the  brain. 

A  year  later  (191 2)  Carlson  and  his  pupils,  using  essentially 
the  methods  of  Morat,  Boldyreff,  Cannon,  and  Washburn,  demon- 
strated on  man  and  experimental  animals  that  a  certain  type  of 
contractions  in  the  empty  or  nearly  empty  stomach  gives  rise  to 


HISTORICAL  29 

the  sensation  of  hunger  by  stimulation  of  sensory  nerves,  not  in 
the  gastric  mucosa,  but  in  the  submucosa  or  muscularis.  These 
hunger  contractions  of  the  empty  stomach  are  primarily  initiated 
in  the  stomach  itself  and  are  thus  independent  of  motor  impulses 
from  the  brain,  or  the  spinal  cord.  The  peripheral  or  gastric  origin 
of  the  essential  element  in  the  sensation  of  hunger  was  thus  finally 
established. 


CHAPTER  III 

THE  STOMACH  IN  HUNGER 
I.      METHODS   OF   INVESTIGATION 

Several  methods  are  available  for  studying  the  tonus  and  con- 
tractions of  the  empty  stomach  both  in  man  and  experimental 
animals,  namely:  (i)  direct  inspection  by  means  of  a  permanent 
opening  (gastric  fistula)  into  the  stomach  through  the  abdominal 
wall;  (2)  the  introduction  of  a  rubber  balloon  into  the  stomach, 
either  through  the  esophagus  or  through  the  gastric  fistula,  and 
recording  the  variations  in  pressure  on  the  distended  balloon  due 
to  contractions  in  the  stomach;  (3)  the  introduction  into  the 
stomach  of  a  balloon  coated  with  bismuth  paste  on  the  inside. 
This  permits  graphic  recording  of  the  stomach  movements  syn- 
chronously with  X-ray  photography  or  inspection  by  aid  of  the 
fluoroscope,  and,  in  man,  recording  the  subjective  sensations. 

In  our  work  all  three  methods  have  been  employed.  During 
the  last  four  years  the  author  has  been  fortunate  in  having  in  his 
service  a  *' second  Alexis  St.  Martin,"  a  man  with  complete  closure 
of  the  esophagus  and  a  permanent  gastric  fistula  of  twenty  years' 
standing.  The  gastric  fistula  is  large  enough  to  permit  direct 
inspection  of  the  interior  of  the  stomach,  and  the  introduction  of 
balloons,  rubber  tubes,  and  small  electric  lights  for  various  investi- 
gations. This  man,  Fred  Vlcek,  a  native  of  Trebone,  Bohemia,  is 
now  thirty-one  years  old.  For  the  last  twenty  years,  or  since  1897, 
,  he  has  fed  himself  through  a  permanent  gastric  fistula  owing  to 
complete  closure  of  the  esophagus,  as  a  result  of  accidentally  drink- 
ing a  strong  solution  of  caustic  soda. 

Previous  to  the  swallowing  of  the  caustic  the  boy  had  always 
been  healthy.  Since  the  completion  of  the  gastric  fistula  in  1897, 
he  has  enjoyed  good  health  except  that  he  suffered  an  attack  of 
pneumonia  in  1908.  Mr.  V.  came  to  America  in  1910.  He  is  in 
good  physical  condition,  height  5  ft.  8  in.;   weight,  62  kg.    With 

30 


THE  STOMACH  IN  HUNGER 


31 


the  exception  of  the  closed  esophagus  and  the  gastrostomy,  the  man 
is  in  every  respect  in  normal  health,  and  of  good  average  physical 
development.  The  size,  form,  and  position  of  the  stomach  is  that 
of  the  "orthotonic"  type.  The  opening  into  the  stomach  is  on  the 
lesser  curvature  about  4  cm.  on  the  fundus  side  of  the  "transverse 
band."  The  fistula  is  large  enough  to  admit  a  rubber  tube  three- 
fourths  of  an  inch  in 
diameter,  and  a  rubber 
tube  of  this  size  is 
always  kept  in  the  fis- 
tula. It  is  usually 
pushed  in  to  a  depth 
of  3  to  4  inches.  The 
outer  end  (about 
3  inches)  is  kept  corked 
and  bent  under  the 
bandage  between 
meals.  The  tube  is 
changed  once  a  month. 
Although  the  tube  fits 
rather  snugly  in  the 
opening,  there  is  at 
times  some  leakage  of 
gastric  juice  around  it, 
and  in  consequence 
some  corrosion  of  the 
skin  for  a  considerable 
area  around  the  tube. 


Fig.  I. — Mr.  F.  V.  Twenty  years  after  perma- 
nent closure  of  the  esophagus  and  establishment  of 
the  gastric  fistula. 


The  stomach  mucosa  joining  the  skin  or  scar  tissue  has  the  same 
appearance  and  seems  to  show  the  same  sensitiveness  as  the  rest 
of  the  stomach  mucosa.  X-ray  photographs  and  direct  inspection 
by  the  fluoroscope  show  that  the  esophagus  is  completely  closed 
at  the  level  of  the  sternum. 

A  normal  person  readily  learns  to  swallow  a  small  rubber  balloon 
with  a  small  flexible  rubber-tube  attachment,  and  to  keep  these  in 
place  for  hours  without  the  least  discomfort  or  annoyance.    There 


32  CONTROL  OF  HUNGER  IN  HEALTH  AND,  DISEASE 

is  some  salivation  to  begin  with,  but  this  soon  ceases.  Adults  as 
well  as  infants  with  this  apparatus  in  the  stomach  and  mouth  find 
no  difficulty  in  going  to  sleep  during  an  observation  period.  It  is 
easier  to  swallow  this  apparatus  than  an  ordinary  stomach  tube, 


Fig.  2. — Photograph  showing  permanent  gastric  fistula  of  Mr.  F.  V.,  with  rubber 
tube  in  situ. 

as  the  latter  is  too  thick  and  inflexible.  The  method  has  been  used 
on  newborn  infants  with  success.  It  is  being  used  in  the  author's 
laboratory  by  graduate  and  medical  students.  The  method  is 
so  readily  mastered  as  to  make  it  generally  available  in  physio- 
logical, psychological,  and  clinical  work.    The  main  points  involved 


THE  STOMACH  IN  HUNGER  33 

are:  (i)  the  selection  of  balloon  and  rubber  tubing  of  proper  size 
and  flexibility;  (2)  the  balloon  and  tube  must  be  swallowed,  not 
pushed  down  into  the  stomach;  (3)  the  avoidance  of  discomfort 
or  aversion  by  proper  training. 

The  stomach  contractions  are  recorded  from  the  balloon  in  the 
stomach  connected  by  a  rubber  tube  with  a  water,  bromoform,  or 
chloroform  manometer.  The  balloons  used  by  us  on  man  varied 
in  capacity  from  75  to  150  c.c.  In  our  observations  on  infants 
balloons  of  smaller  size  were,  of  course,  employed.  And  in  the 
work  of  the  stomach  (rumen)  of  goats,  balloons  of  greater  strength 
and  capacity  are  preferable.  When  bromoform  manometers  were 
used  a  manometer  tube  1.5  cm.  in  diameter  was  found  serviceable. 
The  air  pressure  in  the  balloon  with  the  stomach  at  relative  rest 
was  usually  adjusted  at  3  to  6  cm.  of  bromoform.  After  trying 
out  balloons  of  varying  capacities  and  thickness,  we  concluded 
that  a  condum  of  the  thinnest  rubber  available  in  the  market  was 
the  most  serviceable,  as  this  balloon  when  collapsed  is  easily  swal- 
lowed. The  advantage  of  such  a  delicate  balloon  is  in  recording 
the  weaker  tonus  changes  or  contractions,  and  the  pulse  beat  in  the 
stomach.  The  only  disadvantage  is  the  occasional  breaking  of  the 
balloon  by  an  exceptionally  sudden  and  vigorous  stomach  contrac- 
tion, especially  when  a  bromoform  manometer  is  used  for  recording. 

For  the  convenience  of  the  reader  who  may  not  be  familiar  with 
the  ordinary  technique  of  graphic  registration,  a  diagram  illus- 
trating the  balloon  method  as  used  on  man  is  shown  in  Fig.  4  in 
the  hope  that  it  may  aid  in  interpreting  the  various  stomach 
tracings  reproduced  in  this  and  subsequent  chapters. 

II.      MOVEMENTS   OF   THE  EMPTY   STOMACH  IN  MAN 

The  movements  of  the  empty  stomach  in  mammals  were  exten- 
sively studied  by  Boldyreff  in  dogs  by  means  of  the  gastric  fistula. 
Rubber  balloons  were  introduced  into  the  stomach  and  connected 
by  air  or  water  transmission  to  the  recording  manometer.  Accord- 
ing to  Boldyreff  the  empty  stomach  of  the  dog  exhibits  alternating 
periods  of  complete  quiescence  during  the  first  three  or  four  days 
of  fasting.    The  periods  of  activity  vary  in  length  from  twenty  to 


34 


CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 


thirty  minutes,  and  the  intervening  periods  of  rest  last  from  i^  to  2| 
hours.  Both  the  fundus  and  the  pyloric  region  of  the  stomach  are 
involved  in  the  activity  of  the  contraction  period,  the  fundus  giving 
lo  to  20  very  vigorous  contractions.  Boldyreff  states  definitely — 
and  the  published  tracings  seem  to  support*  the  statement — that 


Fig.  3. — Photograph  showing  arrangements  for  simultaneous  recording  of  the 
gastric  hunger  contractions  and  the  vasomotor  and  cardiac  changes  (arm  plethys- 
mograph)  of  Mr.  F.  V. 


between  the  period  of  strong  rhythmical  contractions  the  stomach 
is  in  complete  rest.  The  period  of  activity  begins  with  weak 
contractions,  and  these  increase  gradually  in  strength  until  the 
period  ends  abruptly  with  the  strongest  contractions.  Inasmuch 
as  the  tracings  pubHshed  by  Boldyreff  do  not  show  the  stomach 


THE  STOMACH  IN  HUNGER 


35 


respiratory  pressure  or  the  stomach  pulse  pressure,  it  would  seem 
that  the  methods  of  registration  were  not  dehcate  enough  to  detect 
feeble  rhythms  of  contractions  that  might  have  been  present  during 
the  periods  of  relative  rest. 

Cannon  and  Washburn  studied  the  movements  of  the  empty 
stomach  in  man  by  introducing  a  balloon  through  the  esophagus 
into  the  stomach.  The  observations  were  made  6  to  20  hours  after 
meals.    They  found  that  the  periodic  activity  of  the  empty  human 


Fig.  4. — Diagram  showing  method  of  recording  gastric  hunger  contractions  of 
the  empty  stomach  of  normal  persons.  B,  rubber  balloon  in  stomach.  D,  kymograph. 
F,  cork  float  with  recording  flag.  M,  manometer.  L,  manometer  fluid  (bromoform, 
chloroform,  or  water).  R,  rubber  tube  connecting  balloon  with  manometer.  S,  stom- 
ach.   T,  side  tube  for  inflation  of  stomach  balloon, 

stomach  is  very  similar  to  that  in  the  dog,  but  the  average  dura- 
tion of  the  periods  is  not  given.  The  fundus  contractions  were 
about  30  seconds  in  duration,  and  the  pause  between  the  contrac- 
tions lasted  about  60  seconds.  The  published  tracings  show  a 
gradual  tonus  contraction  of  the  fundus  during  the  pause.  The 
observations  of  Cannon  and  Washburn  were  mainly  directed 
toward  establishing  the  relation  between  the  contraction  periods 
of  the  stomach  and  the  sensation  of  hunger.  They  seem  to  agree 
with  Boldyreff  in  the  absolute  quiescence  of  the  stomach  between 
the  periods  of  strong  rhythmical  contractions.    ^'Before  the  hunger 


36  CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

was  experienced  by  W.  the  recording  apparatus  revealed  no  sign 
of  gastric  activity."  There  is  some  indication  of  a  feeble  rhythm 
during  the  rest  period  in  one  of  their  published  tracings. 

When  the  pressure  in  the  balloon  in  the  empty  stomach  of  a 
normal  person  is  properly  adjusted  and  the  manometer-recording 
devices  made  as  dehcate  as  possible,  the  tracings  obtained  form 
a  composite  of  the  following  pressure  variations  in  the  gastric 
cavity: 

1.  Periods  of  powerful  rhythmical  contractions,  alternating  with 
periods  of  relative  quiescence.  As  the  duration  of  each  individual 
contraction  in  these  periods  is  approximately  30  seconds,  we  may 
call  these  contractions  the  ^^30-seconds  rhythm."  The  entire  con- 
traction period  we  will  designate,  provisionally,  as  the  ''hunger 
period,"  and  the  individual  contractions  in  the  period  the  ''hunger 
contractions." 

2.  A  tonus  rhythm  (tonus  contraction  of  fundus)  of  wonderful 
uniformity  in  rate,  but  fluctuating  in  ampHtude,  the  rate  varying 
from  18  to  22  seconds  with  an  average  of  20  seconds.  The  tonus 
rhythm  increases  in  amplitude  without  change  in  rate  during  the 
periods  of  the  powerful  rhythmical  contractions  of  the  fundus,  and 
are  weakest  immediately  after  these  periods.  But  they  are  always 
present  in  the  empty  stomach  of  man,  provided  the  subject  is  in 
good  health.  For  the  sake  of  brevity  we  may  designate  these 
contractions  provisionally  as  "20-seconds  rhythm."  The  method 
used  by  Cannon  and  Washburn  was  evidently  not  delicate  enough 
to  detect  this  tonus  rhythm,  and  hence  they  concluded,  erroneously, 
that  the  empty  stomach  of  man  is  completely  quiescent  between 
the  periods  of  the  strong  hunger  contractions. 

3.  A  pulse  pressure  rhythm,  always  present. 

4.  A  respiratory  pressure  rhythm,  always  present. 

The  periods  of  relatively  powerful  rhythmical  contractions 
(30-seconds  rhythm)  are  practically  identical  with  the  periods  of 
"hunger  contraction"  of  Cannon  and  Washburn.  The  individual 
contractions  of  these  periods  usually  begin  as  a  feeble  tonus  rhythm; 
they  gradually  increase  in  amplitude  pari  passu  with  shortening  of 
the  intervening  pauses,  and  may  or  may  not  end  in  tetanus  or 


THE  STOMACH  IN  HUNGER  37 

prolonged  tonus  contractions,  followed  by  a  relatively  abrupt 
relaxation  and  quiescence. 

When  the  contractions  are  relatively  feeble,  the  periods  of 
activity  are  always  short,  the  variation  being  from  6  to  20  minutes, 
with  an  average  duration  of  12  minutes.  The  number  of  strong 
contractions  in  these  periods  varies  from  10  to  25,  with  an  average 
of  about  14  contractions.  The  duration  of  each  individual  con- 
traction is  approximately  20  to  25  seconds.  The  stronger  con- 
tractions are  usually  in  the  middle  of  the  periods,  the  initial  and 
final  contractions  being  the  weakest.  In  no  case  have  we  seen 
such  a  period  end  in  tetanus. 

The  periods  of  more  powerful  contractions  exhibit  some  char- 
acteristic features.  The  periods  are  always  initiated  by  weak 
contractions  with  long  intervening  pauses.  These  pauses  may  be 
of  several  minutes'  duration.  Then,  the  individual  contractions 
gradually  increase  in  amplitude,  and  the  intervening  pauses  become 
shorter,  until  the  climax  is  reached  in  a  number  of  very  powerful 
and  rapid  contractions  approaching  incomplete  tetanus.  The 
tetanus  when  present  usually  lasts  from  2  to  5  minutes.  The  cessa- 
tion of  these  periods  of  activity  is  always  abrupt.  In  Mr.  V.  there 
were  at  times  two  or  three  periods  of  nearly  complete  tetanus  at 
the  end  of  the  period.  On  five  different  days  these  final  tetanus 
periods  lasted  for  from  10  to  15  minutes.  This  is,  however,  excep- 
tional. When  the  period  does  end  in  tetanus,  the  tetanus  usually 
lasts  only  2  to  3  minutes. 

This  ending  of  the  contraction  period  in  an  incomplete  tetanus 
appears  to  be  characteristic  of  young  and  vigorous  individuals. 
In  older  people  the  period  usually  ends  in  a  single  vigorous  con- 
traction without  tetanus,  except  under  certain  conditions.  The 
ending  in  tetanus  appears  to  be  an  evidence  of  relatively  great 
tonicity  of  the  stomach.  In  one  perfectly  Aormal  man  (Mr.  O.) 
on  whom  hundreds  of  observations  were  made,  the  entire  period 
(15  to  20  minutes)  was  virtually  a  nearly  complete  gastric  tetany. 

The  duration  of  each  contraction  varies  from  20  to  30  seconds. 
The  contraction  time  is  shortest  at  the  final  stage  of  greatest 
activity.    When  the  contrary  appears  to  be  the  case,  the  tracings 


38 


CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 


show  that  the  prolonged  curve  is  a  fusion  of  two  or  more  contrac- 
tions. The  interval  between  the  contractions  varies  from  2  to  5 
minutes  at  the  beginning  of  a  period  to  nothing  at  the  end.  The 
duration  of  the  period  varies  from  |  to  i^  hours.  The  usual  run  is 
30  to  45  minutes,  the  longer  periods  being  exceptional,  when  there  is 
no  experimental  interference  with  the  stomach.  The  number  of 
individual  contractions  in  a  period  varies  from  20  to  70.     The  period 


Fig.  5. — The  three  upper  tracings  are  typical  records  of  the  gastric  hunger 
contractions  of  normal  adult  persons  toward  the  end  of  a  hunger  period.  The  tracings 
are  recorded  and  are  to  be  read  from  left  to  right,  and  in  each  case  the  gastric  hunger 
contractions  cease  spontaneously  near  the  right  end  of  the  tracings.  The  more  rapid 
excursions  are  due  to  the  movements  of  respiration.  The  bottom  tracing  shows  typical 
gastric  hunger  contractions  of  a  normal  dog. 

of  relative  motor  quiescence  of  the  empty  stomach  between  the  con- 
traction periods  varies  from  J  to  2I  hours  in  normal  adult  persons. 
A  few  characteristic  records  of  these  strong  periods  of  motor  activity 
of  the  empty  stomach  in  normal  persons  are  shown  in  Fig.  5. 

There  remains  to  be  noted  a  rather  atypical  form  of  activity 
of  the  empty  stomach  occasionally  observed.     This  consists  in 


THE  STOMACH  IN  HUNGER  39 

contractions,  feeble  or  powerful,  that  do  not  fall  into  distinct  groups 
or  periods.  These  contractions  are  usually  irregular  both  in  strength 
and  in  rate.  The  average  rate  is  slow,  the  interval  between  the 
contractions  varying  from  5  to  10  minutes.  Similar  solitary  con- 
tractions may  also  appear  in  the  interval  between  two  typical 
periods  of  rhythm.  These  contractions  may  come  two  or  three 
in  sequence,  typical  of  the  beginning  of  an  activity  period,  but 
instead  of  a  gradually  increasing  activity  the  stomach  relapses 
into  relative  quiescence  for  another  10  to  30  minutes. 

The  reader  may  question  the  accuracy  of  denoting  these  con- 
tractions as  motor  activities  of  the  empty  stomach.  In  all  of  these 
cases  the  stomach  was  certainly  empty  of  food.  But  may  not  the 
distended  balloon  act  as  food,  so  far  as  the  food  acts  mechanically 
in  the  way  of  producing  stomach  movements  ?  This  is,  indeed, 
claimed  to  be  the  case  by  Mangold  for  the  muscle  stomach  of  the 
buzzard.  It  is  not  difficult  to  prove  that  certain  forms  of  mechanical 
stimulation,  such  as  the  sudden  distension  of  a  rubber  balloon  in 
the  gastric  cavity,  may  cause  brief  contractions  in  the  stomach, 
but  it  can  be  shown  just  as  conclusively  that  the  stomach  rhythms 
described  above  are  not  caused  by  the  presence  of  the  foreign  objects 
in  the  stomach. 

1.  The  presence  of  the  distended  balloon  in  the  stomach 
between  the  contraction  periods  does  not  induce  these  con- 
tractions. 

2.  In  Mr.  V.  the  gastric  contractions  can  be  observed  directly 
through  the  large  fistula  without  any  balloon  in  the  stomach. 

3.  The  contraction  periods  come  on  just  as  frequently  without 
any  balloon  in  the  stomach  and  produce  the  same  effect  on  con- 
sciousness (hunger). 

4.  In  pigeons  the  periodic  strong  contractions  of  the  empty 
crop  can  be  seen  directly  through  the  skin  and  a  balloon  in  the  crop 
does  not  alter  their  frequency  or  intensity. 

The  stomach  pulse. — When  the  empty  stomach  is  moderately 
contracted,  direct  inspection  by  the  aid  of  a  small  electric  bulb 
in  the  gastric  cavity  shows  distinct  oscillations  of  the  rugae  syn- 
chronous with  the  arterial  pulse.     The  oscillations  of  the  rugae 


40  CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

cause  similar  oscillations  of  the  gastric  juice  (mixed  with  mucin), 
which  is  always  present  in  the  otherwise  empty  stomach.  When 
the  strong  contractions  (30-seconds  rhythm)  appear,  the  pulse 
oscillations  of  the  rugae  seem  to  disappear,  either  because  of  the 
greater  rigidity  of  the  stomach  folds,  or  else  owing  to  the  difficulty 
of  distinguishing  the  pulse  oscillations  when  the  rugae  are  closely 
packed  and  slide  rapidly  over  and  past  one  another,  as  they  do 
when  the  fundus  contracts.  The  picture  revealed  by  the  gastric 
cavity  when  the  empty  stomach  is  in  a  period  of  rhythmic  con- 
tractions is  interesting,  but  rather  bewildering,  and  we  have 
ceased  to  wonder  how  Beaumont  could  have  so  completely  failed 
to  grasp  the  character  of  the  stomach  movements  in  digestion, 
as  he  relied  mainly  on  such  direct  inspection  of  the  stomach  of 
Alexis  St.  Martin. 

III.      TONUS  AND   CONTRACTIONS   OF   THE  EMPTY   STOMACH 
IN  THE  NEWBORN  INFANT 

The  gastric  hunger  mechanism  is  probably  inherited.  At  any 
rate,  the  frequency  and  duration  of  the  periods  of  gastric  hunger 
contractions  are  related  to  the  feeding  habits  of  the  individuals 
or  the  species  only  so  far  as  the  feeding  time  and  food  quantity  are 
factors  in  the  time  required  for  emptying  of  the  stomach,  and  hence 
for  the  appearance  of  the  hunger  contractions.  On  the  other 
hand,  the  hunger  mechanism  determines  to  a  certain  extent  the 
feeding  habit.  Animals  and  children  probably  eat  as  soon  as  the 
stomach  is  nearly  empty,  if  food  is  at  hand,  and  the  greater 
frequency  of  the  gastric  hunger  periods  in  the  young  is  probably 
related  to  the  more  continuous  feeding  on  the  part  of  the  young 
animal. 

We  have  made  observations  on  a  number  of  newborn  infants, 
with  results  showing  that  the  empty  stomach  at  birth  and  in  the 
prematurely  born  exhibits  the  typical  periods  of  tonus  and  hunger 
contractions  of  the  adult,  the  only  difference  between  infant  and 
adult  being  the  greater  frequency  of  these  periods  in  the  young. 
In  some  of  the  infants  the  observations  were  made  before  their 
first  nursing.     It  is  thus  clear  that  in  the  normal  individual  the 


THE  STOMACH  IN  HUNGER 


41 


gastric  hunger  mechanism  is  completed,  physiologically,  and  is 
probably  active  some  time  before  birth. 

The  recording  of  the  gastric  hunger  contrac- 
tions of  the  newborn  human  infant  offers  no  great 
difficulties,  if  one  uses  dehcate  rubber  balloons  of 
15  c.c.  capacity,  attached  to  a  flexible  rubber 
catheter  of  2  mm.  diameter.  Most  of  the  infants 
swallowed  this  apparatus  without  difficulty  and 
went  to  sleep  in  our  arms  during  the  observation 
periods.  The  results  were  always  most  satisfac- 
tory with  the  infants  asleep,  as  that  eliminated 
all  nervous  inhibitory  factors,  and  the  disturbances 
from  body  movements  and  from  irregularities  in 
respiration.  Practically  nothing  can  be  done  with 
the  balloon  method  if  the  infant  is  at  all  restless. 
All  of  our  observations  were  made  on  healthy  and 
vigorous  infants. 

In  human  infants,  periods  of  gastric  tonus 
and  hunger  contractions  are  in  evidence  shortly 
after  birth  and  before  any  food  has  entered  the 
stomach.  These  gastric  hunger  periods  exhibit  all 
the  pecuHarities  of  the  gastric  hunger  contractions 
of  the  adult,  except  that  the  periods  of  motor 
quiescence  of  the  stomach  between  the  hunger 
periods  are  on  the  whole  much  shorter  (10  to  15 
minutes).  When  the  gastric  hunger  contractions 
become  very  vigorous  the  sleeping  infant  may 
show  some  restlessness,  and  may  even  wake 
up  and  cry.  If  the  infant  is  awake  the  very 
vigorous  hunger  contractions  frequently  induce 
crying  and  restlessness.  A  tracing  showing  a 
typical  hunger  period  in  a  9-hour-old  infant 
before  first  nursing  is  reproduced  in  Fig.  6.  The 
reader's  attention  is  called  to  the  fact  that  in 
infants  the  gastric  hunger  periods  usually  end  in 
incomplete  tetanus,  an  index  of  youth  and  vigorous  stomach 


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42  CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

IV.     MOVEMENTS  OF  THE  EMPTY  STOMACH  IN  DOGS 

The  contractions  of  the  empty  stomach  in  dogs  were  recorded 
by  means  of  a  bromoform  manometer  connected  with  a  dehcate 
rubber  balloon  in  the  stomach.  In  the  dogs  the  balloon  was  intro- 
duced into  the  stomach  either  through  a  gastric  fistula  or  through 
the  esophagus.  We  were  surprised  to  note  the  ease  with  which  a 
small  rubber  balloon  and  rubber-tube  attachment  can  be  passed 
through  the  esophagus  into  the  stomach  in  dogs.  If  gentle  dogs 
are  selected  for  the  work  and  the  dogs  are  handled  gently,  they 
make  little  or  no  resistance  after  the  first  two  or  three  experiments. 
We  have  never  observed  vomiting  or  gagging  in  dogs  as  a  result  of 
the  introduction  or  the  presence  of  the  stomach  tube  in  the 
esophagus.  On  the  contrary,  the  dog  with  the  rubber  tube  and 
balloon  in  the  stomach  and  esophagus  will  lie  quietly  for  hours  in 
the  lap  of  an  attendant,  while  the  tonus  and  movements  of  the 
empty  stomach  are  being  registered  on  the  kymograph.  Frequently 
the  dog  will  go  to  sleep  during  the  experiments.  This  is  especially 
the  case  if  the  dog  is  covered  up  with  a  coat  or  a  comforter.  The 
tube  in  the  esophagus  does  not  cause  distress  or  inhibition  of  the 
stomach  movements.  After  some  training  the  dogs  do  not  even 
chew  or  bite  on  the  rubber  tube  in  the  mouth. 

Some  of  the  observations  were  made  on  dogs  with  a  fistula 
in  the  fundus  of  the  stomach.  In  our  first  dog  we  made  use  of  the 
classical  silver  cannula.  In  all  the  other  dogs  we  discarded  the 
metal  cannula  and  adopted  the  surgical  methods  followed  in 
human  gastric  fistula  cases.  The  incision  (3  to  4  cm.  in  length)  is 
made  3  cm.  below  the  last  rib  and  5  to  6  cm.  to  the  left  of  the  linea 
alba.  The  oblique  and  transverse  muscles  are  carefully  separated 
without  cutting  them.  The  desired  region  of  the  gastric  fundus 
is  pulled  out  through  this  opening.  The  peritoneum  is  sutured 
to  the  fundus  pouch.  The  abdominal  muscles  are  similarly  sutured 
to  the  pouch.  In  making  these  sutures  care  is  taken  not  to  pene- 
trate deeper  than  the  muscle  layers  of  the  pouch.  The  apex  of  the 
fundus  pouch  is  then  slit  open,  and  the  edges  sutured  to  the  edges 
of  the  skin.  A  closed  rubber  tube  i  cm.  in  diameter  is  passed 
through  the  opening  into  the  stomach  and  kept  in  place  for  4  days. 


THE  STOMACH  IN  HUNGER  43 

Then  the  tube  and  dressing  are  removed.  It  is  found  that  the 
abdominal  muscles  compress  this  narrow  pouch  to  such  an  extent 
that  there  is  virtually  no  leakage  from  the  stomach,  much  less 
leakage,  in  fact,  than  even  in  the  most  successful  fistula  using 
the  metal  cannula.  There  is  no  trouble  in  closing  up  of  the 
fistula  as  long  as  the  animal  is  being  used  two  or  three  times  a 
week.  The  dog  takes  care  of  the  slight  leakage,  so  there  is  no 
corrosion  of  the  skin.  We  have  dogs  now  in  the  laboratory  with 
such  fistula  of  18  months'  standing,  and  the  dogs  are  in  the  best 
of  condition.  In  fact,  it  is  obvious  that  this  fistula  leaves  the  stom- 
ach much  more  normal  than  does  the  silver  cannula  method.  We 
have  obtained  normal  hunger  contractions  of  the  empty  stomach 
36  to  48  hours  after  making  the  fistula.  Nothing  like  normal 
hunger  contractions  is  seen  in  the  stomach  for  6  to  10  days  after 
making  the  fistula  by  means  of  the  metal  tube.  The  old  silver 
tube  method  should  be  abandoned  in  all  experimental  work  on 
the  stomach. 

In  the  beginning  of  this  work  the  animals  were  kept  suspended 
in  comfortable  hammocks  during  the  observations  on  the  gastric 
hunger  movements.  It  soon  became  apparent,  however,  that  any 
kind  of  mechanical  restraint  on  a  young,  vigorous,  and  very  hun- 
gry dog  causes  restlessness  and  evident  distress,  especially  when 
continued  for  hours.  Training  will  overcome  this  in  part,  but  not 
completely.  Distress  and  restlessness  will  obviously  interfere 
with  the  stomach  movements.  We,  therefore,  tried  the  expedient 
of  having  an  attendant  keep  the  dog  snugly  in  his  lap  during  the 
observation  period.  This  proved  very  satisfactory,  except  for  the 
attendant.  It  is  irksome,  to  say  the  least,  to  sit  still  for  2  to  8 
hours  at  a  stretch.  We  can  appreciate  the  reason  for  the  dog's 
restlessness  when  restrained  mechanically  in  a  hammock  or  on  a 
couch  for  that  length  of  time.  When  the  attendant  knows  how 
to  handle  dogs,  even  a  very  hungry  dog  will  lie  in  Ivs  lap  quietly 
for  hours,  and  will  usually  cuddle  up  and  go  to  sleep.  After  a 
few  experiments  most  dogs  seek  the  research  room  by  preference, 
and  jump  into  the  attendant's  lap  voluntarily.  Some  of  our  dogs 
became  so  well  trained  that  they  would  lie  quietly  on  a  pillow  for 


44  CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

2  to  3  hours  at  a  time  without  any  restraint  whatever.  It  is  obvious 
that  mental  stress  and  restlessness  interfere  with  the  stomach 
contractions,  not  only  in  the  way  of  direct  inhibition,  but  also 
by  the  varying  tonus  and  irregular  contractions  of  the  abdominal 
muscles.  The  animals  used  in  these  experiments  were  mostly 
young  and  vigorous  females. 

The  contractions  of  the  empty  stomach,  as  registejed  by  means 
of  a  delicate  balloon  in  the  fundus,  fall  into  three  types  according 
to  the  degree  of  tonus  of  the  stomach. 

Type  I:  When  the  stomach  shows  feeble  tonus,  the  hunger 
contractions  show  an  average  duration  of  about  30  seconds,  and 
the  intervals  between  the  contractions  vary  from  ^  to  3  or  4  min- 
utes. This  type  of  contractions  usually  falls  into  groups,  separated 
by  intervals  of  relative  quiescence.  The  duration  of  the  groups 
varies  from  i  to  3  hours,  and  the  number  of  contractions  in  each 
group  varies  correspondingly.  It  is  very  rare  that  a  contraction 
group  of  type  I  ends  in  a  tetanus  so  frequently  observed  in  man. 
The  group  usually  begins  with  feeble  contractions  but  of  longer 
than  average  duration  and  relatively  far  apart,  and  the  contractions 
become  gradually  stronger  and  the  intervals  shorter.  The  end  of 
the  group  is  usually  characterized  by  contractions  of  gradually 
decreasing  strength. 

Type  II:  When  the  stomach  is  in  relatively  strong  tonus  the 
hunger  contractions  follow  one  another  in  rapid  succession,  that 
is,  without  any  intervening  pause.  The  duration  of  the  contractions 
varies  between  20  and  30  seconds.  These  contractions  are  fre- 
quently interrupted  by  periods  of  incomplete  tetanus  lasting  from 
I  to  5  minutes.  These  periods  of  tetanus  are  practially  identical 
with  those  previously  described  in  man.  The  contractions  of  this 
type  do  not  fall  into  distinct  groups.  They  may  vary  to  some 
extent  in  ampHtude  and  rate,  but  otherwise  be  continuous  for  an 
observation  period  lasting  from  2  to  6  hours.  If  the  animal  be- 
comes restless  during  the  observation  period  the  hunger  contrac- 
tions become  irregular  and  may  cease  altogether,  but  this  is  probably 
due  to  splanchnic  inhibition,  and  cannot  be  regarded  as  a  spon- 
taneous cessation  of  the  hunger  contractions. 


THE  STOMACH  IN  HUNGER  45 

This  type  of  hunger  contractions  seems  to  be  present  only  in 
young  and  vigorous  individuals  in  excellent  physical  condition. 
Similar  contractions  were  observed  in  man,  but  less  frequently 
than  in  our  young  and  vigorous  dogs.  From  observations  on  man, 
it  is  certain  that  the  hunger  sensation  is  practically  continuous 
during  these  contractions. 

Type  III:  The  hunger  contractions  designated  as  type  III 
constitute  virtually  an  incomplete  tetanus  of  the  stomach.  This 
tetanus  is  characterized  by  periods  of  strong  and  relatively  persistent 
tonus  on  which  are  superimposed  a  series  of  rapid  contractions. 
The  duration  of  these  rapid  contractions  averages  12  to  15  seconds. 
These  contractions  are  evidently  analogous  to  the  20-seconds 
rhythm  in  man.  These  tetanus  periods  vary  in  length  from  i  to  10 
minutes.  In  prolonged  starvation  they  may  last  much  longer.  In 
moderate  hunger  they  are  interspersed  between  groups  of  the 
type  II  rhythm. 

This  description  of  the  gastric  hunger  contractions  in  dogs  is 
based  on  observations  on  more  than  fifty  individuals.  The  shortest 
observation  period  on  each  animal  was  two  weeks,  the  longest  five 
months  with  records  taken,  on  the  whole,  every  third  day.  The 
data  should  therefore  be  typical.  The  three  types  of  contractions 
may  be  observed  in  the  same  dog  on  different  days,  or  type  I  may 
obtain  for  a  few  days,  and  then  be  superseded  by  type  II,  etc.  As 
a  general  rule  type  I  predominated  in  some  of  the  dogs  and  types, 
II  and  III  in  others.  Some  of  the  tracings  also  disclose  what  may 
be  termed  transition  stages.  Thus,  near  the  end  of  a  contraction 
period  of  type  I  the  rapidity  of  the  contraction  may  approach  that 
of  type  II,  and  occasionally  the  individual  contractions  of  type  II 
will  for  short  periods  slow  up  to  such  an  extent  that  they  parallel 
type  I.  This  is  to  be  expected,  since  the  types  of  the  hunger  con- 
tractions seem  to  vary  with  the  degree  of  gastric  tonus,  and  this 
tonus  may  vary  considerably  during  a  single  observation  period. 
It  is  also  to  be  noted  that  the  hunger  contractions  may  occasionally 
be  feeble,  irregular,  or  practically  absent  for  at  least  2  to  4  hours 
at  a  time  in  dogs  that  are  seemingly  in  good  condition.  And  this  is 
usually  the  case  if  the  dogs  are  in  poor  condition  from  any  cause. 


46  CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

The  credit  of  discovery  of  the  rhythmical  contractions  of  the 
empty  stomach  in  dogs  belongs  to  Boldyrefif,  but  his  account  of  the 
rhythm  is  incomplete  and  partly  misleading.  According  to  Boldy- 
reff  the  contractions  always  come  in  groups  of  20  to  30  minutes' 
duration,  and  during  the  ij  to  2J  hours'  intervals  between  these 
groups  in  which  the  stomach  is  completely  quiescent.  The  con- 
tractions observed  by  Boldyreff  were  evidently  short  and  feeble 
periods  of  the  type  I  contractions,  but  the  duration  of  the  interval 
between  the  contractions  given  by  Boldyreff  is  on  the  whole  much 
greater  than  that  shown  in  my  series.  Boldyreff  evidently  never 
obtained  the  rhythm  of  types  II  and  III  in  his  animals.  The 
difference  in  the  results  of  Boldyreff  and  our  own  are  probably  due 
to  (i)  the  condition  of  the  animals,  (2)  the  method  of  handling  the 
animals,  and  (3)  the  method  of  registering  the  stomach  contrac- 
tions. Boldyreff  used  the  classical  silver  cannula  for  the  gastric 
fistula.  This  depresses  the  stomach.  All  the  dogs  had  in  addition 
to  the  gastric  fistula  (fundus)  also  duodenal,  pyloric,  pancreatic,  or 
hepatic  fistulae.  His  dogs  were  therefore  subjected  to  much 
greater  disturbance  of  digestion  and  metabolism  than  is  the  case 
of  a  simple  fistula  of  the  fundus  as  prepared  by  me.  As  the  dogs 
were  not  in  the  best  of  condition,  it  is  not  surprising  that  they 
showed  only  the  feeble  rhythm  of  type  I.  But  it  seems  likely  that 
forcing  the  dogs  by  mechanical  means  to  lie  or  stand  in  one  position 
for  6  to  1 2  hours  at  a  time  is  also  partly  responsible  for  the  brevity 
of  the  contraction  periods  and  the  length  of  the  intervening  periods 
of  quiescence.  It  is  my  experience  that  dogs  thus  treated  become 
restless,  and  restlessness  always  is  accompanied  by  gastric  inhibi- 
tion, probably  through  the  splanchnics.  When  the  dog  is  allowed 
to  make  himself  comfortable  in  the  lap  of  an  attendant  he  hes 
quietly  and  usually  without  any  restraint.  This  condition  is  cer- 
tainly more  nearly  normal. 

The  tracings  published  by  BoldyrefT  do  not  show  the  respiratory 
intragastric  pressures,  nor  do  they  indicate  the  slightest  variations 
of  the  gastric  tonus  during  the  observation  periods.  His  method 
of  registration  was  therefore  not  delicate  enough  to  detect  small 
variations  in  the  intragastric  pressure.     It  would  seem,  however. 


THE  STOMACH  IN  HUNGER  47 

that  his  method  ought  to  have  recorded  the  type  II  contractions, 
if  they  had  been  present  in  his  dogs. 

V.   MOVEMENTS   OF   THE   RABBIT's   STOMACH  DURING  HUNGER 

Rogers,  working  in  the  author's  laboratory,  made  gastric 
fistulas  in  rabbits  by  opening  the  abdominal  cavity  about  i  inch 
to  the  left  of  the  mid- ventral  line  and  as  close  to  the  costal  border 
as  possible  and  suturing  the  muscularis  of  the  fundic  portion  of 
the  stomach  to  the  peritoneum  and  obhque  muscles  and  then  the 
gastric  mucosa  to  the  skin.  These  fistulas  were  made  rather  small, 
so  that  there  would  be  little  leakage  of  gastric  juice  or  loss  of  food. 
At  times  a  small  rubber  tube  was  inserted  into  the  stomach  and 
left  there  for  longer  or  shorter  times  to  prevent  closing  of  the  fistula. 
Within  36  hours  after  the  operation  the  animals  are  usually  feeding. 
These  rabbits,  if  properly  taken  care  of,  are  in  as  good  condition  as 
normal  animals. 

Graphic  records  were  made  using  the  rubber  balloon  method 
with  a  manometer  pressure  of  2  to  4  cm.  of  chloroform.  Medium- 
sized  adult  rabbits  were  used  in  this  set  of  experiments.  In  no 
case  did  any  animal  survive  a  period  of  continuous  starvation  of 
more  than  7  days.  In  animals  that  died  of  starvation  there  were 
always  considerable  amounts  of  residue  in  the  stomach.  In  the 
moist  condition  in  which  this  was  removed  from  the  stomach  it 
weighed  from  8  to  13  gm.  Normally  the  moist  contents  of  the 
adult  rabbit's  stomach  weigh  90  gm.  or  more.  Soon  after  being 
deprived  of  its  usual  food  the  rabbit  provides  a  substitute  by 
eating  its  own  excreta.  Putting  the  animal  in  a  wire-bottom 
cage  does  not  prevent  this.  The  only  practicable  way  to  pre- 
vent it  is  to  inclose  the  animal  in  a  cage  so  fitted  with  a  lid, 
that  the  rabbit's  head  is  held  outside,  its  body  inside  the  cage. 
No  doubt  such  a  position  proves  very  irksome  to  the  rabbit, 
but  after  becoming  accustomed  to  the  position  the  activities  of 
the  stomach  were  not  inhibited.  In  an  animal  so  fixed,  the 
stomach,  as  noted  by  Swirski,  empties  itself  in  about  24  hours. 
Nevertheless,  during  normal  conditions  of  life  the  rabbit's  stomach 
is  never  empty. 


48 


CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 


Since  normally  the  stomach  is  never  empty,  it  is  to  be  expected 
that  gastric  digestion  peristalsis  will  always  persist.  But  as  the 
period  of  starvation  is  prolonged,  the  stomach  contractions  are 
altered.  Instead  of  being  the  gentle  peristalsis  of  normal  digestion, 
they  become  relatively  powerful  contraction  waves  which  rapidly 
follow  one  another,  with  a  tendency  for  each  peristaltic  wave  to 
pass  into  a  short  period  of  tetany.  There  is  no  indication  of  rest 
or  periodicity  to  these  stronger  contractions  until  a  short  time 


^W'^^^^m^^'WY^  m 


Fig.  7. — Contractions  of  the  rabbit's  stomach,  a,  normal  digestive  peristalsis; 
b,  after  24  hours'  starvation;  c,  after  75  hours'  starvation;  d,  after  92  hours'  starva- 
tion; e,  after  no  hours'  starvation.  The  animal  died  a  few  hours  after  this  tracing  (e) 
was  taken  (Rogers). 


before  death  from  starvation.  Auer  has  pointed  out  that  during 
normal  peristalsis  in  the  rabbit,  the  stomach  is  incessantly  active. 
During  hunger  the  strength  of  these  contractions  is  accentuated. 
Following  this  period  of  increased  activity  during  starvation, 
there  comes  a  period  of  depression.  This  is  coincident  with  marked 
general  weakness  of  the  animal  or  even  coma.  The  decline  in  the 
vigor  of  the  stomach  activities  comes  on  gradually.  The  contrac- 
tions become  weaker,  of  shorter  duration,  and  alternating  with 
short  periods  of  rest.     In  the  last  stage  of  starvation  there  may 


THE  STOMACH  IN  HUNGER  49 

occur  prolonged  contractions  or  periods  of  tetany  lasting  from  2 
to  3  minutes  (Fig.  7). 

Gastric  tonus  variations  were  frequently  seen  during  hunger, 
but  not  commonly  during  normal  digestion  peristalsis.  May  not 
the  increasing  muscle  tone  of  the  stomach,  as  starvation  is  pro- 
longed, play  a  part  in  causing  the  sensation  of  hunger  ?  Certainly 
a  state  of  greater  contraction  of  the  stomach  on  the  substances 
remaining  within  it,  as  starvation  is  prolonged,  is  the  first  apparent 
change.  Rabbits  will  show  signs  of  hunger,  such  as  restlessness, 
gnawing  of  dry  wood,  and  eating  cotton,  before  the  character  of 
the  movements  as  recorded  by  this  method  shows  any  striking 
change  from  the  normal  digestion  peristalsis.  The  increased 
activity  of  the  stomach  that  later  appears  is  no  doubt  also 
accompanied  by  psychic  changes.  The  appearance  of  gastric 
tetany,  if  the  animal  is  still  able  to  move  about,  is  marked  by 
restlessness. 

In  order  to  determine  whether  or  not  the  stomach  of  the  rabbit 
when  it  contains  no  food  is  quiescent,  the  animal  was  so  caged  as 
to  be  excluded  from  its  feces.  The  only  difference  observed  be- 
tween an  animal  so  caged  and  one  free  to  move  about  was  that  the 
increased  vigor  of  the  stomach  contractions  comes  on  sooner  in 
the  former.  In  about  12  hours  after  feeding  the  contractions 
become  very  much  stronger  than  normal  digestion  peristalsis,  and 
this  activity  both  of  contractions  and  tonus  variations  persists 
after  the  stomach  has  emptied  itself  of  food. 

VI.      GASTRIC  HUNGER  CONTRACTIONS   OF  THE   GUINEA-PIG 

Sixteen  animals  weighing  from  450  to  900  gm.  were  studied  by 
Dr.  Helene  King  over  periods  varying  from  13  to  66  days.  The 
guinea-pig  is  so  foreshortened  that  the  gastrostomy  operation  was 
beset  with  some  difficulties — the  fundic  portion  of  the  stomach  is 
pushed  up  under  the  diaphragm  in  such  a  manner  that  it  must  be 
pulled  downward  and  stitched  to  the  abdominal  wall  to  make  a 
fistula,  or  an  opening  must  be  in  the  pyloric  region.  Both  methods 
proved  satisfactory,  and  the  possible  objection  to  the  lower  opening 
that  the  balloon  did  not  lie  in  the  fundus  was  obviated  by  the  use 


50  CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

of  a  small  balloon  or  of  a  finger  cot  from  3  to  5  c.c.  in  capacity, 
pushed  well  up  into  the  stomach.  Several  animals  killed  with  the 
balloon  in  place  left  no  doubt  of  the  ease  with  which  it  was  properly 
inserted.  Very  small  fistulas  were  made  so  that  when  the  wounds 
healed  they  often  measured  less  than  i  cm.  across.  Since  the 
animals  began  eating  within  12  hours,  the  food  in  the  distended 
stomach  prevented  the  openings  from  closing. 

The  guinea-pig,  like  other  herbivorous  animals,  feeds-  at  fre- 
quent intervals — ^probably  every  hour — and  under  normal  conditions 
the  stomach  is  never  found  empty.  Even  within  2  hours  after 
exclusion  from  food  it  begins  eating  its  own  excreta,  a  fact  noted  by 
other  observers,  and  after  12  hours  will  eat  paper,  pasteboard,  or 
anything  of  that  nature  within  reach.  The  easiest  and  most  effec- 
tive method  found  for  excluding  it  from  its  own  feces  was  to  place 
the  body  of  the  animal  in  a  bag,  sufficiently  small  to  prevent  much 
freedom  of  movement,  and  then  to  draw  the  bag  closely  about 
the  neck. 

In  the.  guinea-pig  contractions  of  the  stomach  were  observed  in 
5  hours  after  taking  the  food  away.  Frequently  continuous  records 
were  made  from  the  time  the  food  was  removed  until  the  onset  of 
such  vigorous  movements.  The  mild  peristaltic  waves  of  digestion 
become  more  and  more  intense  until  contractions  such  as  might  be 
classified  as  type  I  appear — that  is,  periods  of  tonus  lasting  2  or  3 
minutes  with  4  or  5  superimposed  contractions.  This  type  may 
continue  for  4  hours,  but  they  gradually  merge  into  the  more  vigor- 
ous type  II  and  possible  type  III.  The  contractions  follow  one 
another  in  rapid  succession — one  in  18  seconds  on  the  average — 
such  a  period  terminating  in  complete  quiescence  of  the  stomach. 
At  times  a  period  of  violent  coughing  precedes  the  inhibition. 
Contractions  of  types  I  and  II  have  been  recorded  continuously 
for  6  hours  with  but  two  periods  of  rest  lasting  8  and  6  minutes 
respectively. 

That  discomfort  is  experienced  by  the  guinea-pig  when  food  is 
withheld  for  even  4  or  5  hours  is  evidenced  by  restlessness,  the 
eating  of  the  animal's  own  excreta,  chewing  movements,  and  some- 
times crying,  when  the  contractions  are  unusually  vigorous.    The 


THE  STOMACH  IN  HUNGER  51 

animal  evidently  experiences  hunger  while  the  stomach  still  con- 
tains an  abundance  of  food. 

VII.      CONTRACTIONS    OF   THE  PARTLY  EMPTY  STOMACH   (rUMEN) 
OF   THE   RUMINATING  ANIMALS 

Like  the  stomach  of  the  herbivora  in  general,  the  various  divi- 
sions of  the  stomach  in  the  ruminants  are  probably  never  completely 
empty  of  food.  Digestion  in  these  animals  is  therefore  a  more  or 
less  continuous  process,  and  if  they  eat  because  feeling  hunger, 
they  must  be  capable  of  experiencing  hunger  with  the  stomach 
partly  filled  with  food,  and  while  the  blood  is  still  receiving  a 
constant  stream  of  digested  pabulum  from  the  small  intestines. 

By  a  balloon  method  and  with  a  fistula  in  the  rumen.  Dr.  Schalk 
and  the  writer  studied  the  contractions  of  this  stomach  pouch  in 
the  goat.  We  started  the  work  on  the  rumen,  as  this  corresponds 
to  the  cardiac  or  fundus  part  of  the  stomach  of  other  mammals, 
and  is,  therefore,  probably  the  region  most  directly  concerned  with 
the  causation  of  hunger. 

The  body  of  the  rumen  of  the  goat  exhibits  strong  periodic 
contractions,  independent  of  those  concerned  with  the  regurgitation 
of  the  food  bolus  into  the  mouth,  i.e.,  the  act  of  rumination.  The 
contractions  vary  in  intensity,  but  appear  to  be  practically  con- 
tinuous; that  is,  there  appears  to  be  no  period  of  real  quiescence. 
When  the  goat  is  starved  for  several  days  or  the  greater  part  of  the 
food  in  the  rumen  is  removed  through  the  fistula,  these  contractions 
become  stronger  without  much  change  in  rate.  So  far,  observa- 
tions have  been  made  only  on  the  rumen  of  one  goat,  but  the  motor 
conditions  found  are  essentially  similar  to  those  already  described 
in  the  rabbit  and  the  guinea-pig.  The  digestion  contractions  of 
the  filled  rumen  pass  gradually  into  the  stronger  contractions  of 
the  empty  or  partly  empty  rumen.  We  may  provisionally  call  the 
latter  ''hunger  contractions,"  assuming  that  it  is  the  partly  empty 
rumen  that  gives  the  impetus  to  feed.  So  far  as  we  know  the  only 
difference  between  the  completely  filled  and  the  partly  empty 
rumen  is  this  difference  in  tonus  and  strength  of  contraction. 
There  is  no  gastric  juice  secreted  in  the  rumen,  hence  there  is  no 


52  CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

acidity  except  that  due  to  the  action  of  bacteria,  and  there  is  no 
regurgitation  of  the  acid  content  of  the  true  stomach  (abomasum) 
into  the  rumen.  Unless  we  assume  with  J.  Muller  that  the  sensa- 
tion of  hunger  is  purely  negative,  or  due  to  the  absence  of  satiety, 
the  hunger  in  the  ruminant  must  in  some  manner  be  associated 
with  these  powerful  contractions  of  the  partly  empty  rumen. 

VIII.      CONTRACTIONS   OF   THE  EMPTY  CROP   IN  BIRDS 

In  normal  pigeons,  with  appetites  satisfied,  the  crop  is  very 
much  distended,  and  only  occasional  contractions  of  the  crop  can 
be  detected  by  means  of  the  balloon  in  the  cavity  (Rogers) .  These 
contractions  cannot  be  detected  by  inspection  of  the  skin  covering 
the  crop.  An  hour  or  two  after  feeding  stronger  contractions  in 
groups  of  3  to  4  appear  at  15-  or  20-minute  intervals.  The  motor 
activity  of  the  crop  is  gradually  increased  until,  8  to  12  hours  after 
feeding,  groups  of  8  to  20  strong  contractions  appear  at  intervals 
of  10  to  30  minutes.  Later  the  crop  of  young  birds  passes  into  a 
state  of  continuous  rhythmical  contractions.  When  the  food  con- 
tent of  the  crop  is  reduced  to  about  one-third  of  the  crop's  capacity, 
the  contractions  are  visible  through  the  skin.  At  this  time  they 
involve  only  the  lower  part  of  the  crop.  When  the  crop  is  com- 
pletely empty  the  contractions  occur  in  periods  of  10  to  60  minutes 
apart,  with  8  to  20  contractions  in  each  group.  The  contractions 
of  the  empty  crop  begin  at  the  upper  end,  and  pass  over  the  entire 
crop  as  a  peristaltic  wave.  Each  contraction  requires  12  to  15 
seconds  to  pass  over  the  crop.  The  balloon  in  the  crop  does  not 
initiate  contractions  unless  the  pressure  is  excessive.  A  small  fistula 
in  the  crop  has  no  effect  on  the  contractions. 

It  is  thus  evident  that  the  empty  or  nearly  empty  crop  of 
gallinaceous  birds  exhibits  periods  of  powerful  contractions  involving 
the  entire  organ,  while  in  the  filled  crop  the  periodic  contractions 
are  confined  to  the  lower  end  of  the  organ  mainly  (Fig.  8,  c). 

Rogers'  studies  on  the  crop  in  the  pigeon  have  not  yet  been 
extended  to  muscular  stomach  or  gizzard.  According  to  Rossi 
the  stomach  of  chickens  shows  greater  motor  activity  when  empty 
than  during  digestion,  but  Mangold  states  that  the  empty  muscle 


THE  STOMACH  IN  HUNGER 


53 


Fig.  8. — a,  tracings  of  the  gastric  hunger  contractions  of  the  empty  stomach  of 
the  bullfrog,  12th  day  of  starvation  (Patterson);  b,  tracing  of  the  gastric  hunger 
contractions  of  the  turtle,  21st  day  of  starvation  (Patterson);  c,  tracing  showing  the 
periodic  hunger  contractions  of  the  crop  of  birds  (pigeon),  2d  day  of  starvation  (Rogers), 


54  CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

stomach  of  the  buzzard  is  quiescent.  Stubel,  on  the  other  hand, 
reports  that  the  empty  muscle  stomach  of  pigeons  and  chickens 
and  ducks  shows  a  rhythmical  action  current,  which  obviously 
implies  a  corresponding  activity  or  rhythm. 

In  the  species  of  birds  with  the  food  reservoir  in  the  esophagus 
(crop),  the  contractions  of  this  region  of  the  esophagus  are  probably 
the  most  important  element  in  the  genesis  of  the  hunger  sensation, 
because  the  crop  is  emptied  sooner  than  the  gizzard. 

IX.      CONTRACTIONS   OF   THE  EMPTY   STOMACH  OF   AMPHIBIA 
AND  REPTILIA 

Observations  (Patterson)  were  made  on  the  bullfrog  (Rana 
caterbiana)  and  the  common  snapping  turtle  (chelydra  serpen- 
tina) by  the  balloon  and  the  balloon  X-ray  method.  In  the  turtles 
the  balloon  was  introduced  through  an  ordinary  gastrostomy  open- 
ing. In  the  frogs  a  stomatotomy  was  made  by  a  small  incision 
between  the  ramus  of  the  inferior  maxillary  and  the  anterior 
coronary  of  the  hyoid  bone  through  the  skin,  the  mylo-hyoid 
muscle,  and  the  mucous  membrane  of  the  throat. 

There  are  slight,  if  any,  tonus  variations  in  the  empty  stomach 
of  frogs  and  turtles.  In  healthy  frogs  the  stomach  exhibits  continu- 
ous rhythmical  contractions.  These  contractions  are  remarkably 
strong,  sustaining  a  column  15  to  22  cm.  high.  The  contraction 
phase  is  abrupt;  the  relaxation  is  slower;  in  fact,  it  proceeds 
until  the  next  contraction.  The  X-ray  studies  in  the  intact 
animal  as  well  as  observations  on  the  isolated  stomach  showed 
that  each  contraction  is  a  peristaltic  wave  starting  at  or  near  the 
cardia  and  sweeping  over  the  entire  stomach,  just  as  is  the  case 
with  the  gastric  hunger  contraction  in  the  mammals.  The  striking 
difference  between  the  bullfrog  and  the  mammal  is  the  absence  of 
periodicity  or  grouping  of  the  frog's  gastric  contractions  (Fig.  8,  a). 

The  amplitude  of  these  contractions  in  the  frog  is  increased 
during  prolonged  starvation,  but  there  is  no  obvious  increase  in 
tonus.  The  contractions  cease  at  temperatures  above  38°  .C.  and 
below  13°  C.  It  is  significant  that  the  cessation  of  the  hunger 
contractions  of  the  empty  stomach  at  low  temperature  (i3°C.)  is 


THE  STOMACH  IN  HUNGER  55 

not  in  tonus,  but  in  atony  of  the  stomach.  It  would  thus  seem 
the  gastric  hunger  mechanism  is  paralyzed  in  the  hibernating  frog. 
The  hunger  contractions  of  the  empty  stomach  of  the  turtle 
are  very  similar  to  those  of  the  bullfrog.  The  rate  of  the  contrac- 
tion is  somewhat  less,  and  there  are  periods  of  relative  quiescence 
of  the  empty  stomach  similar  to  that  in  mammals  and  birds.  In 
prolonged  starvation  the  contractions  become  stronger  and  show 
a  tendency  to  pass  into  short  periods  of  incomplete  tetanus 
(Fig.  8,  b). 


CHAPTER   IV 
THE  STOMACH  IN  HUNGER  {Continued) 

I.      RELATION  BETWEEN  DIGESTION  CONTRACTIONS   OF   THE  FILLED, 
AND   HUNGER   CONTRACTIONS    OF   THE    '' EMPTY"    STOMACH 

As  we  have  seen  in  the  case  of  the  rabbit  and  the  guinea-pig 
and  the  goat,  the  digestion  contractions  of  the  filled  gradually  pass 
into  the  hunger  contractions  of  the  empty  or  nearly  empty  stomach. 
In  the  frog  and  the  turtle  the  digestive  peristalsis  of  the  filled  stomach 
is  practically  identical  with  the  hunger  peristalsis  of  the  empty 
stomach.  What  are  the  conditions  in  man  and  the  higher  carnivor- 
ous mammals  ?  Is  it  likely  that  the  situation  is  different  in  animals 
with  a  stomach  always  more  or  less  filled  with  food  and  in  animals 
with  a  stomach  usually  empty  before  they  experience  hunger  ? 

To  answer  this  question  Rogers  and  Hardt,  working  in  the 
author's  laboratory,  used  the  two  standard  methods  of  investigating 
the  movements  of  the  stomach:  the  rubber  balloon  and  the  X-ray 
methods.  The  balloon  was  swallowed  shortly  after  a  meal,  and 
continuous  graphic  records  of  the  intragastric  pressure  variations 
were  made  until  after  the  onset  of  a  typical  hunger  period.  Soon 
after  eating  an  average  meal  the  subject  of  the  experiment  swal- 
lowed the  balloon  and  put  himself  into  a  comfortable  position, 
either  sitting  in  a  chair  or  lying  on  a  cot.  The  results  were  similar, 
irrespective  of  the  position;  the  best  results  were  obtained  while 
the  subject  was  asleep. 

In  order  actually  to  see  the  hunger  movements,  we  coated  a 
balloon  with  a  bismuth  paste  and  observed  its  movements  in  the 
stomach  with  the  X-ray.  These  balloons  were  prepared  by  painting 
the  outer  wall  of  one  with  a  paste  made  of  bismuth  subnitrate  and 
vaseline.  This  balloon  was  then  inclosed  in  another  of  the  same 
size;  hence  the  two  balloons  were  separated  by  a  thin  wall  of  bis- 
muth paste.  One  is  thus  able  to  make  graphic  tracings  with  simul- 
taneous direct  fluoroscope  observation. 

s6 


THE  STOMACH  IN  HUNGER  57 

Our  records  show  that  the  fundus  is  quiescent  immediately 
after  a  large  meal  has  been  eaten.  The  pressure  upon  the  balloon 
is  maintained  at  a  steady  level.  If  a  light  meal  is  taken,  the  tonus 
variations  may  be  demonstrated  immediately  after  eating.  At 
first  they  are  so  slight  as  to  seem  insignificant,  but  they  increase 
in  vigor  and  are  usually  visible  30  minutes  after  the  meal.  In  one 
experiment  an  unusually  large  meal  was  eaten  and  the  tonus 
waves  were  distinctly  in  evidence  20  minutes  later.  They  increase 
in  intensity  and  may,  but  do  not  always,  become  more  rapid. 
Each  wave  is  of  i  to  3  minutes'  duration.    When  the  stomach  is 


Fig.  9. — Tracing  showing  the  tonus  rhythm  of  the  stomach  (man)  3  hours  after 
dinner  (beefsteak,  spaghetti,  bread,  butter,  apples  and  cream,  milk). 

nearly  empty  (as  determined  by  the  stomach  tube  or  induced 
vomiting)  they  become  conspicuous,  and  at  this  stage  of  the 
digestion  there  usually  appear,  superposed  upon  them,  stronger 
contractions  which  increase  in  vigor  and  are  felt  by  the  subject  as 
hunger  pains.  Although  it  is  by  no  means  always  the  case,  it  is 
significant  that  the  first  contractions  felt  as  a  hunger  pang  in  man 
may  occur  when  the  stomach  still  contains  traces  of  food. 

We  have  seen  that  the  onset  of  a  hunger  period  is  marked  by 
the  appearance  of  a  slow  tonus  rhythm  which  gradually  increases 
in  vigor  and  culminates  in  the  hunger  contractions.  This  tonus 
rhythm  is  present,  not  only  as  an  immediate  precursor  of  the  hunger 
period,  but  also  throughout  the  course  of  normal  gastric  digestion. 


58 


CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 


Other  workers  have  employed  the  rubber  balloon  in  recording 
the  digestion  movements  in  the  stomach,  but  none  of  the  pubHshed 
tracings,  so  far  as  we  are  aware,  indicate  the  presence  during 
normal  digestion  of  the  slow  continuous  rhythm  here  described. 
Moritz  reported  contractions  of  the  fundic  end  of  the  stomach 
occurring  2J  to  3^  times  per  minute.     According  to  Dietlan  the 


Fig.  10,  A. — X-ray  photograph  of  the  appearance  of  the  bismuth-coated  balloon 
in  the  stomach  (man)  when  the  empty  stomach  is  quiescent. 


time  required  for  the  peristaltic  contractions  of  the  pyloric  end 
of  the  stomach  is  20  to  24  seconds.  The  tracings  of  Moritz  prob- 
ably record  the  intragastric  pressure  variations  due  to  the  pyloric 
peristalsis.  Sick,  using  the  balloon  method,  describes  tonus  varia- 
tions of  the  fundic  end  of  the  stomach  which  give  rise  to  the  peris- 
taltic waves.    These  occur  at  the  rate  of  2  to  4  per  minute  in  the 


THE  STOMACH  IN  HUNGER  59 

full  or  empty  stomach.  The  tracings  of  Sick  show  three  kinds 
of  pressure  variations:  respiratory,  cardiac,  and  ^'Magen  tonus 
schwangungen,"  the  latter  averaging  20  seconds  each  in  duration. 
The  duration  of  these  ''stomach  tonus  variations"  coincides  with 
the  time  intervals  required  for  the  pyloric  peristalsis. 

Is  the  hunger  contraction  simply  an  augmented  peristaltic  con- 
traction or  a  contraction  of  the  fundus  as  a  whole?    To  answer 


P'iG.  10,  B. — X-ray  photograph  of  the  bismuth-coated  balloon  in  the  stomach 
(man)  at  the  height  of  a  gastric  hunger  contraction  (gastric  hunger  pang)  (Rogers 
and  Hardt). 

this  question  the  stomach  movements  of  the  dog  and  in  man  were 
studied  by  the  ''balloon-X-ray"  method.  We  were  able  to  make 
direct  observations  of  the  movements  of  the  balloon  in  the  stomach 
and  at  the  same  time  to  note  the  character  of  the  graphic  record. 
The  upper  part  of  the  balloon  was  held  in  the  cardiac  end  of  the 
stomach.  A  young  and  vigorous  dog  was  employed  for  the  experi- 
ments.   The  dog  was  starved  for  intervals  of  36  to  48  hours,  and 


6o  CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

in  order  not  to  have  the  hunger  contractions  completely  inhibited 
by  the  excitement  attendant  upon  the  X-ray  examination,  frequent 
repetitions  were  made  until  the  dog  became  accustomed  to  the 
necessary  manipulations.  The  vigor  of  the  stomach  contractions 
thus  made  visible  to  the  naked  eye  is  surprising.  The  weaker 
type  of  hunger  contractions  begin  as  a  constriction  in  the  cardiac 
end  of  the  stomach  and  pass  down  toward  the  pyloric  end  as  a 
rapid  peristaltic  wave.  In  the  very  vigorous  contractions  the 
wave  spreads  over  the  stomach  so  rapidly  that  it  is  difficult  to 
decide  whether  there  is.  a  contraction  of  the  fundus  as  a  whole  or  a 
very  rapid  peristalsis.  This  contraction  may  well  be  compared 
to  the  peristaltic  rush  of  the  intestine  as  described  by  Meltzer  and 
Auer. 

The  balloon-X-ray  observation  of  the  hunger  contractions  was 
made  on  Mr.  R.  when  in  a  reclining  position.  When  a  hunger 
pang  was  felt,  and  the  recording  manometer  showed  the  typical 
rise  in  the  intragastric  pressure,  a  series  of  constrictions  were  seen 
passing  rapidly  over  the  balloon.  Beginning  at  the  cardiac  end, 
they  swept  rapidly  toward  the  pyloric  end,  increasing  in  strength 
as  they  proceeded.  It  was  readily  seen  that  the  hunger  contrac- 
tions are  powerful  peristaltic  contractions,  which,  arising  at  or  near 
the  cardiac  sphincter,  swept  downward  over  the  entire  stomach. 
During  a  typical  hunger  period  the  stomach  exhibits  movements 
which  resemble  very  closely  the  movements  which  have  been 
described  by  some  clinicians  in  patients  after  a  bismuth  meal  as 
hyperperistalsis,  but  described  by  Cole  as  normal  peristalsis  of  a 
stomach  that  contains  small  quantities  of  food.  Observations  on 
the  dog  were  made  after  36  hours  of  deprivation  of  food,  on  man 
after  15  hours.  Prolonged  starvation  in  the  case  of  the  dog  was 
necessary  to  overcome  the  inhibitory  influence  of  the  excitement 
attendant  upon  the  X-ray  examination.  Whether  or  not  the  stom- 
ach of  man  after  3t  long  period  of  starvation  would  show  a  condition 
approaching  that  described  for  the  dog,  we  are  not  in  a  position 
to  state. 

The  current  teaching  with  reference  to  the  part  played  by  the 
fundus  during  digestion  is  that  it  is  a  reservoir,  exerting  a  tonic 


THE  STOMACH  IN  HUNGER 


6i 


grasp  upon  its  contents.  The  kinematographic  figures  of  the 
stomach  published  by  Kastle,  Ridder,  and  Rosenthal  show  that 
the  fundus  is  not  quiescent  during  digestion.  Cole  has  shown  that 
when  food  is  in  contact  with  the  cardiac  end  of  the  stomach  in 
man,  contractions  begin  in  the  fundus  and  frequently  are  as  deep 


mBm^mmmmmmmm 


Fig.  II. — Hunger  contractions  of  the  dog's  stomach  30  hours  after  a  meal. 

A,  outline  of  bismuth-coated  balloon  in  stomach  between  the  gastric  contractions; 

B,  outline  of  balloon  at  the  height  of  a  hunger  contraction  (Rogers  and  Hardt). 


in  this  region  as  in  the  pylorus.  According  to  Forsell,  with  the 
subject  in  the  standing  position,  the  fundus  shows  no  peristalsis. 
In  the  reclining  position  there  occur  typical  peristalses  of  the 
fornix.  At  the  conclusion  of  gastric  digestion  there  occur  circular 
contractions  of  the  wall. 


62  CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

It  is  thus  evident  that  the  digestion  contractions  of  the  filled 
stomach  pass  gradually  over  into  the  hunger  contractions  of  the 
empty  stomach.  This  explains  how  the  hunger  sensation  may  be 
aroused  by  the  stomach  contractions  before  the  stomach  is  actually 
empty.  It  is  merely  a  question  of  intensity  of  the  fundus  contrac- 
tions. But  it  is  still  true  that  the  digestion  contractions  are  pri- 
marily concerned  with  the  pyloric  end  of  the  stomach,  while  the 
hunger  contractions  of  the  empty  stomach  are  initiated  at  the 
cardia  and  involve  the  entire  stomach. 

II.      ORIGIN  OF   THE  HUNGER   SENSATION 

We  have  now  discussed  in  some  detail  the  tonus  and  the  con- 
tractions in  the  empty  or  partly  empty  stomach,  esophagus,  and 
intestine  of  man  and  of  a  number  of  other  species  of  vertebrates. 
Do  these  contractions  initiate  the  sensation  of  hunger,  does  the 
central  state  or  sensation  of  hunger  initiate  the  contractions,  or  is 
there  no  genetic  relation  between  the  two  series  ?  We  have  seen 
that  these  questions  have  been  answered  in  various  ways  by  physi- 
ologists, psychologists,  and  clinicians,  but  without  conclusive  proofs. 

We  owe  the  actual  demonstration  of  the  synchrony  of  the 
hunger  sensations  with  the  strong  contractions  of  the  empty 
stomach  to  Cannon  and  Washburn.  These  observers  recorded  by 
means  of  an  electric  signal  the  subjective  sense  of  hunger  simul- 
taneously with  the  intragastric  pressure,  and  found  that  the 
stomach  contractions  and  hunger  sensations  ran  parallel.  The  fact 
that  the  beginning  of  the  stomach  contractions  is  in  evidence 
before  the  hunger  sensation  is  felt  and  that  the  sensation  lasts 
longer  than  the  active  phase  of  the  contraction  is  adduced  by 
them  in  support  of  the  view  that  contractions  in  some  way  stimu- 
late afferent  nerves  in  the  stomach,  and  that  these  impulses  give 
rise  to  the  hunger  pangs. 

The  beautiful  demonstration  of  Cannon  and  Washburn  leaves 
undecided  the  question  where  the  contraction  stimuli  act  in  the 
stomach,  and  the  cause  of  the  peculiar  periodicity  of  these  con- 
tractions. But  there  can  be  no  further  question  of  the  parallel 
between  the  stomach  contractions  and  the  hunger  sensation,  even 


THE  STOMACH  IN  HUNGER  63 

though  the  evidence  that  the  former  are  the  cause  of  the  latter  is 
incomplete.  We  do  nbt  appreciate  the  force  of  Cannon's  argument 
that  no  other  condition  than  the  contractions  as  the  cause  can 
account  for  the  periodicity  or  intermittency  of  the  hunger  sensa- 
tions. Assuming  that  the  stomach  contractions  constitute  the 
primary  stimuli  in  the  genesis  of  hunger,  does  that  really  solve  the 
problem  of  periodicity  ?  It  would  seem  that  the  problem  is  only 
shifted  a  little;  for  these  stomach  contractions  must  depend  on 
corresponding  periodic  rhythmical  activities  in  the  gastric  muscles 
(idio-muscular  contractions,  ''nodal  tissue"  rhythm)  or  in  central 
or  peripheral  motor  nervous  mechanisms.  That  such  rhythm 
should  give  rise  to  the  hunger  sensations  indirectly  through  con- 
tractions in  the  digestive  tract  is  just  as  difficult  to  explain  as  a 
similar  central  nervous  rhythm  giving  rise  to  or  constituting  the 
hunger  sensation  directly. 

In  our  experiments  the  subject  was  either  standing,  sitting,  or 
lying  down.  His  position  was  such  that  he  could  not  see  the 
kymograph  or  any  of  the  recording  apparatus.  The  signal  key  or 
keys  for  recording  the  hunger  sensation  were  placed  in  his  hand, 
and  he  was  instructed  to  press  the  key  as  soon  as  he  felt  hunger 
and  to  keep  on  pressing  it  till  the  hunger  was  no  longer  felt.  There 
was  no  difficulty  in  keeping  a  person's  attention  fixed  on  this  for 
shorter  periods  of  i  or  2  hours  and  under  conditions  of  hunger 
of  moderate  intensity.  But  in  the  case  of  Mr.  V.,  when  the  obser- 
vations were  continued  without  interruption  for  5  to  6  hours  and, 
therefore,  during  several  periods  of  strong  hunger,  he  would 
usually  become  restless,  and  unable  to  give  undivided  attention 
to  the  introspection. 

Most  of  the  observations  were  made  within  a  period  of  from 
4  to  10  hours  after  meals,  and  only  a  few  as  long  as  24  to  120 
hours  after  a  meal,  for  the  reason  that  the  hunger  pains  in  many 
persons  become  gradually  severe  to  the  point  of  discomfort,  and 
the  man  becomes  restless  and  tired. 

As  a  check  on  the  intragastric  respiratory  pressure,  records  of 
the  respiratory  movements  (chest  pneumograph)  were  usually 
taken  simultaneously  with  that  of  the  stomach  movements. 


64  CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

The  general  results  of  our  work  on  more  than  fifty  men  are  in 
complete  accord  with  those  of  Cannon  and  Washburn.  When  the 
empty  stomach  shows  strong  contraction,  the  subject  invariably 
signals  that  he  feels  hunger,  and,  on  being  questioned,  he  invariably 
repHes  that  he  feels  the  hunger  in  his  stomach.  There  is,  on  the 
whole,  a  fairly  close  correspondence  between  the  duration  of 
stomach  contractions  and  duration  of  the  subjective  sensations  of 
hunger.  On  days  when  the  stomach  does  not  exhibit  these  strong 
contractions,  the  person  does  not  feel  hungry.  These  *' hunger 
contractions"  of  the  empty  stomach  are  primarily  those  of  the 
strong  periodic  rhythm  already  described. 

Relation  between  the  strength  of  the  stomach  contractions  and  the 
intensity  of  the  hunger  sensation. — Data  on  this  point  were  obtained 
in  the  following  manner:  Three  signal  magnets  were  arranged  to 
record  on  the  drum  perpendicularly  to  the  recording  point  of  the 
bromoform  manometer,  and  the  corresponding  keys  were  placed 
in  the  subject's  hand.  He  was  then  instructed  to  press  key  No.  i 
when  he  felt,  without  question,  even  the  faintest  hunger;  No.  2 
when  he  felt  hunger  of  moderate  strength;  and  No.  3  when  he 
felt  the  strongest  hunger. 

The  subject  presses  key  No.  i  (weak  hunger)  at  the  beginning 
of  a  contraction  period  when  the  individual  contractions  are  rela- 
tively feeble.  Then,  as  the  contraction  increases  in  strength,  there 
comes  a  period  of  vacillation  between  key  No.  i  and  key  No.  2 
(moderate  hunger).  As  the  contractions  grow  still  stronger,  key 
No.  2  is  used  for  a  while  without  any  change.  Then  follows  a 
period  of  alternation  between  key  No.  2  and  key  No.  3,  and  in 
the  final  stage  of  maximum  activity  of  the  contraction  period  the 
signal  is  made  with  key  No.  3  exclusively.  In  other  words,  there  is 
a  fairly  close  correspondence  between  the  strength  of  the  stomach 
contractions  and  the  degree  of  hunger  sensations  experienced 
simultaneously. 

This  account  applies  particularly  to  the  first  hunger  period 
appearing  after  a  meal  and  for  the  milder  hunger  periods  in  general. 
On  more  prolonged  fast,  that  is,  after  having  experienced  several 
hunger  periods  in  succession,  the  subject  may  not  signal  with  key 


THE  STOMACH  IN  HUNGER  65 

No.  I  at  all,  and  sometimes  not  even  with  key  No.  2,  but  starts  in 
with  key  No.  3  (strongest  hunger)  at  the  very  beginning  of  a  period, 
despite  the  fact  that  the  strength  of  the  stomach  contractions  is 
not  greater  (or  might  be  even  less)  than  those  designated  as  very 
mild  or  moderate  hunger  some  hours  or  days  earHer.  This  seems 
to  indicate  an  increa'sed  excitability  of  the  afferent  nerves  in  the 
stomach,  or  an  increased  excitabihty  of  some  parts  of  the  brain. 

The  close  parallel  between  the  degree  of  the  stomach  contrac- 
tions and  the  intensity  of  the  hunger  sensations  is  further  shown 
by  the  fact  that  the  beginning  of  a  strong  contraction  is  frequently 
signaled  by  key  No.  2  (moderate  hunger),  and  then  a  shift  made  to 
key  No.  3  (strong  hunger)  nearer  the  apex  of  the  contraction. 
Evidently,  it  is  possible  to  distinguish  a  gradually  increasing 
intensity  of  the  hunger  sensation  during  and  parallel  with  the 
individual  hunger  contractions  in  the  stomach.  But  this  distinc- 
tion is  never  made  in  very  strong  hunger  and  corresponding 
contractions. 

Fusion  of  the  hunger  sensations  into  hunger  tetanus  parallel  with 
strong  and  rapid  contractions  or  tetanus  of  the  stomach  contractions. — 
Th^  essential  features  and  conditions  of  the  incomplete  tetanus  of 
the  stomach  contraction  at  the  end  of  the  period  of  very  vigorous 
contractions  are  already  familiar  to  the  reader.  These  tetanus 
periods  of  the  stomach  are  invariably  accompanied  by  a  similar 
fusion  or  tetanus  of  the  hunger  sensation.  The  fusion  of  the  hun- 
ger sensation  appears  to  be  more  complete  than  the  fusion  of  the 
stomach  contractions.  When  the  rate  of  the  strong  stomach  con- 
tractions approaches  2  per  minute,  the  fusion  of  the  hunger  sensa- 
tions is  practically  complete,  that  is,  a  person  is  then  unable 
to  distinguish  any  rhythmical  variations  in  the  hunger  intensity. 
These  phases  of  the  stomach  contractions  are  always  signaled  with 
key  No.  3  (strongest  hunger).  The  greater  fusion  of  the  hunger 
sensations  than  is  shown  by  the  synchronous  stomach  contractions 
is  probably  due  to  the  tonus  element,  as  a  strong  and  persistent 
state  of  tonus  gives  rise  to  a  continuous  hunger  sensation.  The 
fact  that  the  strong  individual  sensations  lag  or  persist  longer  than 
the  corresponding  stomach  contractions  may  also  be  a  factor. 


66  CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

The  abrupt  cessation  of  the  gastric  tetanus  at  the  end  of  a 
strong  contraction  period  is  accompanied  by  an  equally  abrupt 
and  complete  cessation  of  the  hunger  sensations. 

Individual  contractions  of  the  "20-seconds  rhythm"  may  give 
rise  to  a  mild  hunger  pang,  in  which  case  they  are  usually  stronger 
than  those  not  definitely  recognized  in  consciousness.  But  occa- 
sionally there  may  be  no  marked  difference  in  the  amplitude  of 
the  contractions.  Each  consecutive  contraction  of  the  "  20-seconds 
rhythm"  is  never  signaled  as  a  hunger  contraction  unless  the  con- 
tractions are  very  strong,  in  which  case  they  can  hardly  be 
distinguished  from  the  moderate  contraction  of  the  periodic  or 
*'30-seconds  rhythm." 

Assuming  that  the  "20-seconds  rhythm"  is  an  antrum  rhythm, 
and  that  the  stomach  contractions  cause  the  hunger  sensations, 
it  follows  that  strong  contractions  of  the  pyloric  region  should 
cause  hunger.  Now,  such  strong  contractions  of  this  region  of  the 
stomach  occur  during  vomiting,  yet  vomiting  is,  to  our  knowledge, 
never  accompanied  by  hunger  sensations,  although  epigastric  pain 
and  distress  may  be  felt.  Of  course  it  is  possible  that  the  change 
in  the  physiological  condition  in  the  central  and  the  gastric  nervous 
mechanisms  usually  present  in  vomiting  may  account  for  the 
absence  of  hunger.  The  recognition  of  only  an  occasional  contrac- 
tion of  the  ''20-seconds  rhythm"  as  a  hunger  contraction  when  all 
the  contractions  are  of  nearly  uniform  intensity  is  probably  due  to 
variations  in  attention. 

The  significance  of  the  time  relations  between  the  stomach  contrac- 
tions and  the  hunger  sensations. — It  was  pointed  out  by  Cannon  and 
Washburn  that  the  time  relations  between  the  stomach  contractions 
and  the  hunger  sensations  might  serve  to  determine  the  nature  of 
their  causal  relationship.  It  is  doubtful,  however,  whether  the 
data  secured  by  the  methods  so  far  employed  are  of  much  signifi- 
cance as  regards  this  point.  Unless  the  balloon  in  the  stomach 
completely  fills  the  stomach  cavity  and  the  pressure  in  the  balloon 
is  very  slight,  it  is  clear  that  the  manometer  does  not  register  the 
very  beginnings  of  the  contractions.  And  on  the  subjective  side 
we  have  the  fluctuation  of  attention  as  a  source  of  error. 


THE  STOMACH  IN  HUNGER  67 

The  recognition  of  the  stomach  contraction  as  a  hunger  pang 
depends  not  only  on  the  strength  of  the  contraction,  but  also  on 
the  rapidity  of  development  of  the  contraction  phase;  that  is,  two 
contractions  may  indicate  equal  degrees  of  shortening  of  the  stom- 
ach musculature,  but  if  the  contraction  phase  of  one  covers  a 
minute  or  more,  while  that  of  the  other  half  a  minute  or  less,  the 
latter  contraction  only  is  accompanied  by  a  definite  hunger  sensa- 
tion. The  stomach  may  thus  exhibit  slow  tonus  undulations  of 
considerable  magnitude  without  any  attendant  hunger  feeling. 
This  relation  of  the  rate  of  the  contraction  of  the  hunger  sensation 
is  in  accord  with  one  of  the  general  "laws  of  stimulation,"  and 
would  seem  to  strengthen  the  view  that  the- sensation  is  the  result 
of  the  contraction. 

In  no  instance  out  of  the  numerous  tests  made  on  man  was  the 
hunger  felt  before  the  beginning  of  the  stomach  contractions. 
But  when  the  balloon  and  the  manometer  are  adjusted  as  delicately 
as  possible,  the  hunger  signal  and  stomach  contractions  appear 
nearly  simultaneously.  But  inasmuch  as  the  manometer  probably 
does  not  register  the  very  beginning  of  the  contractions,  it  is  evident 
that  some  seconds  of  the  contraction  phase  always  precede  the 
hunger  feeling. 

When  the  stomach  contraction  is  of  moderate  strength  and 
hunger  sensation  of  correspondingly  moderate  intensity,  the  hun- 
ger sensation  usually  ceases  at  the  height  of  the  contraction,  but 
when  the  contractions  are  very  strong  the  hunger  sensation  persists 
also  during  the  relaxation  phase.  In  other  words,  the  sensation 
lags,  both  at  the  beginning  and  at  the  end  of  the  contraction. 

A  certain  degree  of  constant  or  tonic  contraction  in  the  empty 
stomach  appears  to  give  rise  to  a  continuous  hunger  sensation. — This 
sensation  is  a  somewhat  incomplete  feeling  of  tension  or  pressure 
in  the  epigastric  region,  but  usually  less  intense  and  less  definitely 
localized  than  the  pangs  of  hunger  caused  by  the  strong  rhythmical 
contractions.  This  constant  epigastric  tension  may  thus  be  present 
during  an  entire  hunger  period  lasting  for  15  to  60  minutes  or  more, 
but  augmented  to  distinct  hunger  pangs  with  each  strong  contrac- 
tion.   The  degree  of  tonus  or  constant  contraction  of  the  stomach 


68  CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

during  a  hunger  period  differs  with  the  individual  man,  and  this 
tonus  is  not  in  evidence  in  some  of  the  lower  animals.  But  it  is 
likely  that  close  introspection  will  reveal  uniformly  both  the  longer 
hunger  rhythms  (15  minutes  to  i|  hours)  and  the  more  rapid 
rhythm  (30  seconds)  of  the  hunger  pangs. 

The  stomach  contractions  give  rise  to  the  hunger  sensations. — The 
consideration  of  the  cause  of  the  gastric  hunger  contractions  will  be 
taken  up  later,  but  the  simpler  question  of  the  action  of  the  con- 
tractions may  be  briefly  dealt  with  now.  Assuming,  for  the  present, 
that  the  stomach  contractions  give  rise  to  the  hunger  sensations 
through  the  action  of  afferent  nerves  from  the  stomach,  in  what 
way  does  the  contraction  act  as  a  stimulus  to  these  nerves  ?  Does 
the  hunger  sensation  arise  (i)  from  the  stimulation  of  nerves  in 
the  mucosa;  (2)  from  the  stimulation  of  nerves  in  the  muscular 
coats  and  in  the  connective  tissue;  or  (3)  is  it  due  to  an  inter- 
central  discharge  from  the  Auerbach's  plexus  to  the  brain,  asso- 
ciated with  the  motor  discharge  from  the  same  plexus  to  the 
stomach  musculature  ? 

As  regards  the  first  possibiHty,  the  following  experiments  have 
been  made,  with  negative  results.  It  would  seem  that  the  only 
way  in  which  contraction  of  the  stomach  musculature  can  stimulate 
nerve-endings  in  the  mucosa  is  by  mechanical  pressure.  This  may 
be  imitated  in  the  following  way  on  Mr.  V.  During  the  period  of 
relative  quiescence  of  the  stomach  between  two  periods  of  strong 
hunger,  when  the  afferent  nerves  concerned  are  in  such  condition 
that  their  stimulation  will  give  rise  to  hunger,  mechanical  pressure 
on  the  mucosa  by  distension  of  the  balloon  or  rubbing  the  mucosa 
by  the  closed  end  of  a  test  tube  never  causes  sensations  of  hunger 
unless  these  procedures  lead  to  contractions.  Mr.  V.  always 
stated  that  he  felt  these  pressures,  but  the  sensations  were  not  like 
hunger.  The  objection  might  be  raised  against  these  experiments 
that  the  pressure  is  not  sufficiently  strong,  and,  in  the  case  of  the 
test  tube,  does  not  touch  a  sufficiently  large  area  of  the  mucosa. 
We  admit  that  a  more  intense  mechanical  stimulation  of  the  mucosa 
could  be  produced  by  Pavlov's  method  on  dogs  of  blowing  sand 
into  the  stomach  by  bellows.    But  we  have  not  felt  justified  in 


THE  STOMACH  IN  HUNGER  69 

using  similar  procedures  on  Mr.  V.  The  methods  used  do  not, 
of  course,  produce  the  strongest  possible  mechanical  stimulation 
of  the  mucosa,  but  these  stimulations  were  sufficient  to  affect 
consciousness.  They  were  perceived,  but  not  as  hunger  sensations. 
It  seems,  therefore,  highly  probable  that  the  afferent  nerves  in 
the  mucosa  are  not  primarily  concerned  in  the  genesis  of  the 
hunger  sense.  They  are,  however,  concerned  in  the  inhibition  of 
hunger. 

The  hunger  sensation  seems  to  be  produced  by  the  contractions 
only.  When  the  empty  stomach  is  normal,  strong  contractions,  how- 
ever caused,  produced  a  sensation  of  hunger.  .  Thus,  if  the  balloon 
in  the  stomach  is  rather  suddenly  distended,  this  may  produce 
one,  two,  or  three  strong  contractions  of  the  previously  quiescent 
stomach,  and  these  are  recognized  as  hunger  contractions  identical 
with  those  of  the  ''spontaneous"  hunger  periods.  It  seems  to 
us  that  this  experiment  constitutes  a  demonstration  of  the  periph- 
eral genesis  of  hunger,  as  the  subjective  state  clearly  is  induced 
by  the  peripheral  change.  A  tracing  illustrating  this  phenomena 
is  reproduced  in  Fig.  12. 

But  how  do  the  contractions  stimulate  the  afferent  nerves  in 
the  muscle  layers  ?  Contraction  in  skeletal  muscle  stimulates 
afferent  nerve  fibers  in  the  muscle.  But  it  seems  to  us  that  the 
pain  experienced  from  contractures  or  "cramps"  in  skeletal  muscles 
and  in  the  intestines  in  the  case  of  colic  or  tenesmus  is  somewhat 
different  from  the  hunger  pangs,  even  though  pain  is  inherent  in 
hunger.  The  difference  may  be  only  an  apparent  one;  due  to  the 
fact  that  the  latter  pains  arouse  the  memories  of  previous  agreeable 
experiences  with  food.  Because  of  the  folding  of  the  mucosa  and 
the  submucosa  into  rugae  and  the  changes  in  the  arrangement 
of  the  cells  in  the  muscle  layers  in  the  stomach  during  contractions, 
there  must  be  a  great  variation  in  tension  on  the  nerve-fibers  in 
the  contracted  and  in  the  relaxed  condition  of  the  stomach  walls. 
This  variation  in  tension,  rather  than  actual  pressure,  may  con- 
stitute the  stimulus,  so  far  as  the  stimulus  is  a  mechanical  one. 
Hunger,  therefore,  contains  elements  of  kinesthetic  sensation  as 
well  as  pain,  the  latter  predominating  in  strong  hunger. 


70 


CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 


We  have  been  strongly  impressed  by  Mr.  V.'s  ability  to  recog- 
nize feeble  stomach  contractions  as  hunger  states.  Very  strong 
stomach  contractions  can  be  recognized  as  separate  hunger  pangs 
by  most  people,  but  there  are  great  individual  variations  in  the 
ability  to  recognize  each  individual  contraction,  unless  the  con- 
tractions are  very  strong. 


'^^''''A^^^^^^^'-^ 


B  m^^^^^^^-mmrkikm^ 


Fig.  12. — Two-thirds  the  original  size,  yl,  stomach  contractions;  ZJ,  respiratory 
movements;  a,  b,  signals  for  moderate  and  strong  hunger  respectively.  The  pressure 
in  the  balloon  is  slight.  There  is  no  evidence  of  strong  stomach  contractions,  and  Mr.  V. 
feels  no  hunger.  At  x  the  pressure  in  the  balloon  is  suddenly  increased.  This  disten- 
sion of  the  balloon  initiates  a  few  strong  stomach  contractions,  which  in  turn  cause 
the  hunger  states.    A  demonstration  of  the  gastric  genesis  of  hunger. 


Two  explanations  of  Mr.  V.'s  unusual  ability  in  recognizing  the 
stomach  activities  haVe  occurred  to  the  writer.  Since  early  boyhood 
the  stomach  has  been  to  Mr.  V.  the  object  of  special  care  and  atten- 
tion. In  consequence  of  such  special  attention  to  the  stomach  the 
afferent  nervous  impulses  from  the  stomach  may  attain  a  clearer 
definition  in  consciousness  analogous  to  the  remarkable  development 


THE  STOMACH  IN  HUNGER  71 

of  analysis  in  the  tactile  or  pressure  senses  in  the  absence  of  vision. 
That  this  type  of  education  or  training  does  take  place,  the  author 
is  satisfied  from  his  own  experience  during  the  four  years  that  he 
has  studied  the  hunger  mechanism  on  himself.  At  the  point  of 
the  gastrostomy  Mr.  V.'s  stomach  adheres  to  the  parietal  peri- 
toneum: There  may  be  adhesions  of  greater  extent  in  consequence 
of  the  operation.  The  hunger  sensation  of  Mr.  V.  may  therefore 
include  a  greater  degree  of  pain  than  is  the  case  in  normal  men, 
as  the  contracting  stomach  may  pull  on  the  parietal  peritoneum, 
which,  according  to  many  observers,  is  very  sensitive  to  painful 
stimuli.  The  weaker  stomach  contractions  may  thus  be  recog- 
nized as  hunger  because  more  painful  than  under  normal  conditions. 
Confirmatory  evidence  (or  the  opposite)  ought  to  be  obtainable 
without  much  difficulty,  as  cases  of  gastrostomy  are  fairly  common. 
Clinicians  having  such  cases  in  hand  would  do  a  service  to  physi- 
ology if  they  could  determine  whether  gastrostomy  invariably 
augments  the  hunger  sensations  or  makes  the  hunger  pangs  more 
painful. 

We  have  shown  that  in  all  animals  so  far  studied  the  empty  or 
partly  empty  stomach  exhibits  the  tonus  and  contractions  which 
in  man  give  rise  to  the  hunger  sensation.  There  are  some  differ- 
ences in  these  contractions  in  different  species,  but  these  are 
probably  of  minor  importance.  Manknows  that  asensationof  strong 
hunger  is  felt  synchronously  with  the  strong  contraction.  We  have 
a  right  to  conclude  that  the  lower  animals  experience  the  same 
sensation  simultaneously  with  the  corresponding  contraction.  We 
have,  then,  in  the  tonus  and  contractions  of  the  empty  stomach  an 
objective  criterion  for  the  presence  or  absence  of  hunger  in  experi- 
mental animals  in  normal  health. 

III.      THE  ESOPHAGUS  AND   THE   CARDIA  IN  HUNGER 
I.  METHODS   OF  INVESTIGATION 

There  is  some  evidence  in  the  literature  of  contractions  of  the 
esophagus  synchronous  with  the  periods  of  gastric  hunger  con- 
tractions.   Some  people  refer  the  hunger  sensation  or  hunger  pangs, 


72  CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

not  only  to  the  stomach,  but  also  to  the  chest  and  throat.  This 
appears  to  be  true,  not  only  of  ignorant  people,  such  as  those 
interrogated  by  Schiff,  but  also  of  persons  of  special  training  in 
introspection.  Cannon  and  Washburn  have  described  periodic 
contractions  of  the  lower  end  of  the  esophagus  in  man,  and  these 
contractions  seemed  to  give  rise  to  hunger  pangs  just  as  in  the 
case  of  the  contractions  of  the  empty  stomach.  They  suggest 
that  the  esophagus  contractions  are  synchronous  with  the  gastric 
hunger  contractions,  but  they  did  not  prove  the  hypothesis  by 
recording  the  stomach  and  esophagus  contractions  simultaneously. 

We  studied  the  motor  conditions  of  the  esophagus  in  hunger  on 
three  men  who  experienced  no  difficulty  in  swallowing  simul- 
taneously the  gastric  and  the  esophageal  balloons  with  their  flexible 
rubber  tube  attachments.  In  part  of  the  work  we  used  the  best 
quality  of  rubber  condums  also  for  the  esophagus  balloon,  not  in 
their  entire  length,  as  in  the  case  of  the  stomach,  but  cut  down  to 
a  length  of  3  to  4  cm.  We  soon  encountered  difficulties  in  the  work 
with  the  esophagus,  difficulties  apparently  not  noticed  by  Cannon 
and  Washburn.  Thinking  that  part  of  these  difficulties  might  be 
due  to  the  diameter  of  the  esophagus  balloon,  we  resorted  to  the 
rubber  finger  cot  employed  by  these  observers.  But  even  the 
best  rubber  finger  cots  are  not  as  satisfactory  as  the  condum 
balloon. 

The  position  of  the  balloon  in  the  esophagus  was  usually  deter- 
mined by  the  distance  from  the  incisor  teeth  to  the  lower  end  of 
the  balloon.  If  the  balloon  is  clear  above  the  cardia  the  movements 
of  inspiration  decrease  the  positive  pressure  in  the  distended  bal- 
loon in  proportion  to  increase  in  the  negative  pressure  in  the 
thoracic  cavity.  But  if  the  balloon  is  located  in  the  region  of  the 
cardia  itself,  it  depends  on  the  relative  preponderance  of  diaphragm 
and  chest  movements  whether  the  act  of  inspiration  leads  to  increase 
or  decrease  in  the  balloon  pressure.  The  esophagus  balloon  can  be 
well  in  the  cardia  and  still  show  negative  pressure  in  inspiration 
if  the  inspiration  is  predominantly  costal.  On  the  other  hand,  if 
the  lower  end  of  the  balloon  is  just  within  or  at  the  cardiac  orifice, 
a  diaphragmatic  inspiration  increases  the  pressure  in  the  balloon, 


THE  STOMACH  IN  HUNGER  73 

although  not  to  the  same  extent  as  when  the  balloon  is  in  the 
fundus  of  the  stomach. 

In  the  case  of  A.  J.  C.  and  J.  H.  L.  it  was  found  that  when 
the  distance  from  the  lower  end  of  the  esophagus  balloon  to  the 
incisor  teeth  was  15I  to  16  inches  the  balloon  was  as  far  down  as 
it  could  be  located  without  being  directly  affected  with  the  con- 
tractions of  the  cardia  and  the  stomach.  Allowing  the  balloon  to 
slip  down  ^  to  I  inch  farther  brought  it  to  the  cardia  and  the 
cardiac  end  of  the  stomach.  In  the  case  of  A.  B.  L.  the  distance 
from  the  incisor  teeth  to  the  lower  end  of  the  balloon  could  not 
exceed  14I  to  15  inches,  if  pure  esophagus  effects  were  to  be 
obtained.  When  the  esophagus  balloon  is  located  14  to  16  inches 
from  the  incisor  teeth,  it  is  obviously  well  below  the  level  of  the 
heart,  and  therefore  in  the  region  of  myenteric  plexus  and  non- 
striated  musculature  of  the  esophagus. 

The  esophageal  and  stomach  tubes  were  usually  joined  together 
firmly,  so  that  the  lower  end  of  the  esophagus  balloon  was  ij 
inches  above  the  upper  end  of  the  stomach  balloon.  The  pressure 
in  the  esophagus  balloon  varied  between  i  and  4  cm.  of  chloroform. 

2.  RESULTS  IN  MAN 

Local  contractions  and  peristalsis. — When  the  esophagus  balloon 
is  distended  with  a  pressure  of  2  to  4  cm.  chloroform  the  esophagus 
usually  exhibits  rapid  continuous  contractions.  These  contrac- 
tions are  at  times  quite  regular  both  in  rate  and  amplitude.  The 
total  time  of  each  contraction  is  less  than  2  seconds. 

In  addition  to  these  contractions  the  esophagus  may  show 
contractions  of  a  tonic  character.  The  duration  of  these  contrac- 
tions varies  from  a  few  seconds  to  several  minutes.  If  these  tonus 
contractions  are  only  moderately  strong,  the  rapid  contractions, 
just  mentioned,  continue  and  are  superimposed  on  the  former. 
In  some  cases  the  tonus  contractions  are  quite  regular  in  rate  and 
intensity,  but  this  is  exceptional. 

Both  types  of  contractions  appear  to  be  local.  They  are  not 
related  to  esophageal  peristalsis,  although  a  peristalsis  (caused  by 
swallowing)  may  induce  them  in  a  quiescent  esophagus.    They  are 


74  CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

not  related  to  gastric  contractions,  for  they  occur  when  the  empty 
stomach  is  quies'cent.  They  may  also  occur  during  gastric  hunger 
contractions,  but  in  this  case  there  is  no  synchrony  between  the 
gastric  and  the  esophageal  contractions.  They  are  local  contrac- 
tions of  the  esophageal  tube  and  not  peristaltic,  because  they  do 
not  move  the  distended  balloon.  But  occasional  peristaltic  con- 
tractions of  local  origin  appear  during  these  contractions.  This 
is  shown  by  the  pull  on  the  tube  if  this  is  fixed  to  the  teeth,  or  by 
the  downward  movement  of  the  tube  if  it  is  not  fixed.  In  this  way 
the  esophagus  balloon  is  worked  through  the  cardia  unless  the 
tube  is  secured  to  the  teeth.  This  peristalsis  is  obviously  identical 
with  the  '^ secondary  esophageal  peristalsis"  of  Meltzer. 

These  esophageal  contractions  do  not  give  rise  to  hunger  and  are 
in  no  way  associated  with  this  sensation.  The  rapid  contractions 
do  not  affect  consciousness,  but  more  prolonged  tonic  contractions 
are  felt  if  they  are  strong  or  moderately  strong.  They  are  felt,  not 
as  hunger  pangs,  but  as  a  fulness  in  the  chest  or  throat,  as  of  some- 
thing having  stuck  in  the  throat.  This  sensation  is  so  character- 
istic and  distinct  that  there  is  no  possibiHty  of  confusing  it  with 
hunger  pangs  of  gastric  origin. 

These  contractions  are  caused  by  the  local  mechanical  stimu- 
lation of  the  distended  balloon.  The  contractions  are  more  marked 
the  greater  the  pressure  in  the  balloon,  but  at  times  they  appear 
even  with  a  balloon  pressure  of  less  than  i  cm.  chloroform.  They 
are  most  marked  immediately  after  the  introduction  and  distension 
of  the  balloon,  but  they  may  persist  during  an  entire  observation 
period  of  4  to  5  hours  if  the  balloon  pressure  is  above  i  to  2  cm. 
chloroform.  We  did  not  observe  any  decrease  in  these  local  con- 
tractions during  the  progress  of  the  experiments,  as  one  might  have 
expected  in  case  there  was  any  appreciable  ''education"  of  the 
esophagus  to  the  pressure  of  the  balloon.  Evidently  the  esophagus 
mechanisms  are  so  adjusted  that  local  mechanical  stimulation 
causes  local  contractions  interspersed  with  occasional  peristalsis 
until  the  stimulus  is  removed,  that  is,  the  material  forced  into  the 
stomach.  The  local  contractions  as  well  as  the  secondary  peristalsis 
may  be  reflexes  via  the  medulla,  as  indicated  by  Meltzer's  observa- 


THE  STOMACH  IN  HUNGER  75 

tions.  But  the  absence  of  the  contractions  after  section  of  the  vagi 
does  not  prove  it,  at  least  for  the  part  of  the  esophagus  provided 
with  non-striated  musculature  and  myenteric  plexus.  It  is  known 
that  this  part  of  the  esophagus  responds  to  local  stimulation  with 
local  contractions  and  peristalsis  after  recovery  from  the  temporary 
hypo  tonicity  following  section  of  both  vagi. 

These  local  contractions  of  the  esophagus  were  evidently  not 
encountered  by  Cannon  and  Washburn,  although  the  only  differ- 
ence between  our  technique  and  theirs  is  the  additional  balloon  in 
the  stomach  (and,  in  consequence,  two  rubber  tubes  in  the  esopha- 
gus). Is  the  local  excitability  of  the  esophagus  increased  by  the 
presence  of  a  distended  balloon  in  the  stomach,  a  rubber  tube  in 
the  cardia,  and  a  second  rubber  tube  in  the  esophagus  and  mouth  ? 
All  the  men  used  in  our  experiments  showed  these  contractions. 
Can  it  be  the  esophagus  of  Mr.  Washburn  is  exceptional  ?  Or  did 
Cannon  and  Washburn  have  the  esophagus  balloon  actually  located 
in  the  cardia,  so  that  their  tracings  record  the  behavior  of  the 
cardia  rather  than  that  of  the  esophagus  proper  ? 

Boldyreff  pointed  out  that  the  balloon  method  cannot  be  used 
for  recording  the  periodic  contractions  of  the  empty  intestines,  for 
the  reason  that  the  distended  balloon  causes  local  contractions 
through  mechanical  stimulation.  Fortunately  this  is  not  true  for 
the  gastric  fundus,  but  it  is  true  for  the  esophagus,  at  least  to  an 
extent  to  impair  greatly  the  efficacy  of  balloon  method.  For  when 
the  esophagus  balloon  is  distended  sufficiently  to  register  the 
slightest  tonus  variations  and  contractions  of  the  esophagus,  the 
local  contractions  are  most  prominent  and  disturbing. 

Contractions  synchronous  with  the  gastric  hunger  contractions. — 
The  weaker  gastric  hunger  contractions  at  the  beginning  of  a 
hunger  period  are  usually  not  accompanied  by  any  esophageal 
contractions.  But  synchronous  with  the  strong  hunger  contrac- 
tions that  mark  the  culmination  of  a  gastric  hunger  period  there 
is  some  persistent  increase  in  the  tonus  of  the  esophagus  and  brief 
contractions  simultaneously  with  the  individual  stomach  contrac- 
tions. This  increased  tonus  and  rhythmic  contractions  of  the 
esophagus  parallel  with  the  hunger  activity  of  the  stomach  are  in 


76  CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

evidence  even  when  the  esophagus  exhibits  the  rapid  local  contrac- 
tions described  above.  The  esophagus  contractions  appear  to  lag 
behind  the  gastric  contractions  and  are  as  a  rule  of  briefer  duration. 
The  frequent  culmination  of  the  gastric  hunger  contractions  in  a 
period  of  incomplete  tetanus  of  varying  durations  seems  to  have  no 
parallel  in  the  esophagus  in  the  way  of  strong  and  prolonged 
contractions. 


Fig.  13. — Simultaneous  records  from  the  stomach  (lower  curve)  and  the  lower 
fourth  of  the  esophagus  (upper  curve)  of  A.  J.  C.  during  the  culmination  of  a  period  of 
vigorous  gastric  hunger  contractions.  Lower  end  of  esophageal  balloon  =  16  cm.  from 
incisor  teeth,  that  is,  at  the  cardia.  Pressure  in  balloon  =  3  cm.  chloroform.  Showing 
weak  esophageal  contractions  synchronous  with  the  gastric  hunger  contractions. 
One-half  original  size. 

These  esophageal  contractions  parallel  with, the  gastric  hunger 
contractions  are  apparently  not  identical  with  the  esophageal  con- 
tractions reported  by  Cannon  and  Washburn.  These  observers 
noted  that  the  esophageal  contractions  were  more  prolonged  than 
the  gastric  contractions  of  the  same  man  during  other  hunger 


THE  STOMACH  IN  HUNGER  77 

periods.  The  contractions  noted  by  us  are  usually  briefer  than  the 
parallel  stomach  contractions.  Washburn  was  able  to  associate 
the  esophageal  contractions  with  the  sensation  of  hunger  pangs. 
None  of  us  are  able  to  do  that.  In  the  first  place  the  esophageal 
contractions  that  occur  spontaneously  during  quiescence  of  the 
empty  stomach  contractions  that  may  be  identical  in  rate  and 
strength  with  those  parallel  with  the  gastric  hunger  contractions 
are  either  not  felt  at  all,  or  else  felt  as  a  disagreeable  fulness  in 
the  throat,  something  stuck  in  the  esophagus,  and  not  as  the  uncom- 
fortable emptiness  that  characterizes  the  genuine  pangs  of  hunger. 
To  be  sure,  when  the  gastric  hunger  contractions  are  sufficiently 
intense  to  be  definitely  accompanied  by  esophageal  contractions 
all  of  us  feel  the  pangs  of  hunger  strongly,  but  these  are  of  gastric 
origin  and  are  referred  to  the  stomach  and  not  to  the  esophagus 
or  throat. 

Contractions  of  the  cardia. — That  there  is  an  increase  of  the 
tonic  contraction  of  the  cardia  during  the  gastric  hunger  contrac- 
tions is  rendered  probable  by  the  fact  that  the  air  and  other  gases 
always  present  in  the  stomach  are  not  forced  into  the  esophagus 
during  these  contractions  even  when  they  are  very  strong.  Cannon 
and  Washburn  state  that  this  fact  argues  for  contractions  of  the 
esophagus  parallel  with  the  contractions  of  the  empty  stomach. 
Did  they  not  overlook  the  fact  that  the  cardia  is  capable  of  doing 
this  even  in  the  absence  of  esophageal  contractions  ?  There  is  no 
escape  of  air  from  the  stomach  during  the  periods  of  incomplete 
gastric  tetanus  at  the  end  of  a  hunger  period,  although  these  con- 
tractions are  practically  never  accompanied  by  any  esophageal 
contractions.  In  the  dog  esophageal  contractions  are  known  to  be 
permanently  abolished  by  section  of  both  vagi,  yet  this  does  not 
lead  to  belching  of  air  even  during  the  greatest  increase  in  intra- 
gastric pressure  that  the  contractions  of  the  empty  stomach  are 
capable  of  producing. 

It  is  therefore  evident,  not  only  that  the  cardia  itself  is 
able  to  prevent  the  escape  of  air  into  the  esophagus  during 
increased  intragastric  pressure,  but  also  that  the  cardia  in 
all    probability   contracts   more   powerfully  during    the    gastric 


78  CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

hunger  contractions,  thus  increasing  its  efficiency  as  a  guard. 
Direct  graphic  evidence  of  the  latter  is,  however,  difficult  to 
secure. 

When  the  empty  stomach  is  quiescent  the  cardia  offers  only 
slight  resistance  to  the  withdrawal  of  a  distended  balloon  of  the 
size  of  a  rubber  finger  cot  from  the  stomach  into  the  esophagus. 
A  larger  balloon,  such  as  the  condum  used  for  the  stomach,  en- 
counters somewhat  greater  resistance  at  the  cardia,  as  well  as  in 
the  esophagus  itself.  If  one  attempts  to  withdraw  the  balloon 
from  the  stomach  at  the  height  of  a  gastric  hunger  contraction, 
the  resistance  offered  by  the  cardia  is  distinctly  increased.  This 
can  mean  only  one  thing,  viz.,  an  increase  in  the  contraction  of 
the  cardia.  If  the  contraction  of  the  cardia  did  not  increase,  the 
withdrawal  of  the  balloon  would  be  actually  facilitated  by  the  pres- 
sure exerted  by  the  stomach  contractions.  For  example,  increasing 
the  intragastric  pressure  by  forcible  contraction  of  the  abdominal 
muscles  may  force  the  stomach  balloon  into  the  esophagus  in  case 
the  stomach  is  quiescent. 

It  is  difficult  to  keep  an  inflated  balloon  actually  in  the  cardia 
for  any  considerable  time,  especially  during  the  strongest  gastric 
hunger  contractions.  Strong  esophageal  peristaltic  movements 
keep  pushing  it  toward  the  stomach,  and  at  times  the  gastric  con- 
tractions actually  push  it  back  into  the  esophagus.  At  the  best 
the  balloon  will  stay  in  the  cardia  during  two  or  three  successive 
gastric  contractions  of  the  weaker  type,  that  is,  at  the  beginning 
of  the  hunger  period.  The  type  of  balloon  used  for  these  tests  was 
the  rubber  finger  cot  3  cm.  in  length.  A  balloon  of  greater  length 
could,  of  course,  be  lodged  in  the  cardia  with  greater  ease,  but  a 
balloon  of  greater  length  than  3  cm.  would  be  influenced  not  only 
by  the  cardia,  but  also  by  the  cardiac  ends  of  the  stomach  and  the 
esophagus.  In  fact  this  probably  occurs,  but  to  a  less  extent,  even 
when  a  short  balloon  is  used,  as  the  physiological  cardia  is  probably 
less  than  i  cm.  in  width.  Anatomically  the  cardia  is  not  sharply 
differentiated  in  man.  We  judged  the  position  of  the  balloon  in 
the  cardia  by  the  distance  of  the  balloon  from  the  incisor  teeth  and 
by  the  influence  of  the  respiratory  movements,  moderate  inspira- 


THE  STOMACH  IN  HUNGER  79 

tion,  mainly  costal,  causing  lowered  tension,  and  moderate  dia- 
phragmatic inspiration  causing  increased  tension.  When  the 
balloon  is  in  this  position  the  cardia  exhibits  the  20-seconds 
rhythm  previously  reported  for  the  fundus  of  the  empty  stomach. 
This  rhythm  of  the  cardia  is  in  evidence  even  when  the  empty 
stomach  is  quiescent.  When  the  empty  stomach  shows  hunger 
contractions  the  cardia  shows  parallel  contractions  or  periods  of 
increased  tonus.  The  contractions  of  the  fundus  and  of  the  cardia 
are  strictly  synchronous,  but  those  of  the  cardia  appear  to  be  more 
persistent  or  tetanic.  The  tracings  secured  by  us  from  the  balloon 
in  the  cardia  resemble  those  pubHshed  by  Cannon  and  Washburn 
as  esophageal  contractions  more  than  do  the  actual  esophageal 
contractions  obtained  by  us. 

Contractions  of  the  upper  end  of  the  esophagus. — In  a  few  experi- 
ments the  esophageal  balloon  was  placed  in  the  esophagus  7  to  10 
inches  from  the  incisor  teeth,  that  is,  in  the  lower  part  of  the  neck 
and  upper  part  of  the  chest.  The  spontaneous  local  contractions 
are  in  evidence  also  in  this  part  of  the  esophagus.  There  is  usually 
a  slight  increase  of  tonus  when  very  strong  gastric  hunger  contrac- 
tions are  present,  but  nothing  like  the  strength  of  contractions 
during  the  peristalsis  of  deglutition  or  those  caused  by  the  local 
mechanical  stimulation.  The  tonus  increase  of  the  upper  half  of 
the  esophagus  parallel  with  the  gastric  contractions  is  insignificant 
compared  with  the  corresponding  contractions  of  the  lower  third  of 
the  esophagus.  This  is  probably  correlated  with  the  gradual  dis- 
appearance of  non-striated  musculature  and  myenteric  plexus  in 
the  oral  half  of  the  esophagus  in  man. 

3.  RESULTS   ON  DOGS 

All  of  our  dogs  used  in  this  work  were  provided  with  a  gastric 
fistula  for  the  introduction  of  the  stomach  balloon.  The  esophagus 
was  left  intact  and  the  esophageal  balloon  introduced  through  the 
mouth.  The  dog  is  of  special  interest  in  this  connection,  because 
the  dog's  esophagus  is  composed  of  striated  musculature  throughout 
its  whole  length.  The  myenteric  plexus  is  probably  lacking.  It 
is  needless  to  say  that  all  the  dogs  were  subjected  to  preliminary 


8o  CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

training  in  the  way  of  getting  used  to  the  balloons  in  stomach  and 
esophagus.  As  a  matter  of  fact  all  the  dogs  were  accustomed  to 
these  procedures,  having  been  used  for  other  lines  of  work  on  the 
hunger  mechanism,  so  that  they  would  He  quietly  and  comfortably 
in  the  lap  of  an  attendant  during  the  tests.  It  is  absolutely  essen- 
tial that  the  dogs  be  quiet,  if  possible  sleeping,  during  these  tests, 
for  restlessness  increases  the  disturbance  of  the  esophagus  even 
more  than  of  the  stomach. 

Local  spontaneous  contractions. — The  presence  of  the  inflated 
balloon  in  any  region  of  the  esophagus  caused  rapid  local  contrac- 
tions, more  rapid  than  those  of  the  human  esophagus,  alternating 
with  an  occasional  peristalsis,  also  of  local  origin,  and  occasionally 
more  prolonged  tetanic  contractions.  These  tetanic  contractions 
usually  last  for  only  half  a  minute  to  a  minute.  In  one  case  it 
lasted  15  minutes.  Tetanic  spasms  lasting  up  to  5  minutes  are 
not  uncommon.  These  contractions' have  no  relation  to  the  hun- 
ger contractions  of  the  empty  stomach,  as  they  may  appear  during 
a  hunger  period  as  well  as  during  gastric  quiescence.  They  depend 
on  the  local  stimulation  of  the  balloon  in  the  esophagus  and  are, 
therefore,  more  marked  the  greater  the  tension  in  the  balloon. 
They  are  also  more  marked  when  the  dogs  are  excited,  evidently 
owing  to  increased  reflex  excitability  of  the  medullary  centers  and 
some  increase  in  the  tonus  of  the  esophagus.  The  disturbance  is 
greatest  when  the  balloon  is  first  introduced,  but  it  may  keep  up 
for  hours  even  when  the  pressure  in  the  balloon  is  only  2  to  3  cm. 
of  bromoform  or  chloroform.  A  single  swallowing  act  may  induce 
these  local  contractions,  lasting  for  many  minutes,  in  a  quiescent 
esophagus.  The  same  thing  has  been  observed  in  man.  It  is 
probably  due  to  increased  reflex  excitability  of  the  medulla  and  to 
increased  tonus  of  the  esophagus,  as  the  latter  is  equivalent  to  in- 
creased tension  in  the  balloon,  and  therefore  increased  strength 
of  the  local  mechanical  stimulation. 

When  the  esophagus  contracts  in  tetanus  on  the  balloon,  addi- 
tional disturbing  factors  appear.  Evidently  this  kind  of  contrac- 
tion causes  the  same  sensation  in  man  and  dog,  that  is,  the  feeling 
of  something  stuck  in  the  throat,  for  when  these  contractions 


THE  STOMACH  IN  HUNGER  8l 

are  present  the  dogs  become  restless  and  sometimes  swallow 
repeatedly. 

Condition  of  the  esophagus  during  gastric  hunger  contractions. — 
The  gastric  hunger  contractions  are  not  accompanied  by  contrac- 
tions or  changes  of  tonus  in  any  part  of  the  esophagus.  If  the 
gastric  hunger  contractions  are  very  intense,  so  that  they  cause  the 
dog  to  moan  or  swallow,  contractions  may  appear  in  the  quiescent 
esophagus,  but  this  is  obviously  due  to  the  general  disturbance  of 
the  animal.  There  is  no  synchrony  between  the  gastric  and  the 
esophageal  contractions.  If  the  dog  lies  quietly  or  is  sleeping,  a 
strong  gastric  hunger  period  may  run  its  course  without  the  least 
evidence  of  esophageal  contractions. 

Inhibition  of  the  gastric  hunger  contractions  during  the  tetanic 
contractions  of  the  esophagus. — The  strong  and  prolonged  local 
contractions  of  the  esophagus  cause  inhibition  of  the  gastric  tonus 
and  the  gastric  hunger  contractions,  while  the  rapid  esophageal  con- 
tractions seem  to  have  no  effect  on  the  stomach.  This  is  evidently 
a  special  instance  of  the  "law  of  the  intestine,''  that  is,  inhibition 
caudal  or  aboral  to  a  region  in  the  state  of  contraction.  Other 
factors  may  also  be  concerned  in  this  inhibition  of  the  stomach. 
The  tetany  of  the  esophagus  causes  some  distress,  and  this  may 
lead  to  inhibitory  action  via  the  splanchnic  nerves.  The  gastric 
inhibition  ordinarily  lasts  as  long  as  the  tetanus  in  the  esophagus. 

Contractions  of  the  esophagus  in  response  to  seeing  and  smelling 
food. — Seeing  and  smelling  meat  on  the  part  of  a  hungry  dog  ahnost 
invariably  led  to  contractions  of  the  otherwise  quiescent  esophagus. 
Ordinarily  the  contractions  are  of  the  local  rapid  type,  and  the 
disturbance  of  the  esophagus  lasts  only  for  lo  to  30  seconds.  But 
occasionally  the  sight  or  smell  of  food  may  send  the  esophagus 
into  complete  tetanus  lasting  for  several  minutes.  Both  types  of 
esophageal  contractions  are  accompanied  by  inhibition  of  the 
stomach.  A  single  act  of  swallowing,  as  we  have  seen,  may  produce 
the  same  disturbance  in  the  part  of  the  esophagus  where  the  bal- 
loon is  located,  and  the  dog  frequently  swallows  or  at  least  elevates 
the  larynx  at  the  sight  of  the  food.  But  these  contractions  on  the 
sight  of  food  also  appear  when  the  dog  does  not  swallow.     The 


82  CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

phenomenon  is  probably  to  be  explained  as  follows :  The  sight  or 
smell  of  food  on  the  part  of  the  hungry  dog  causes  temporary 
increase  in  neuro-muscular  tonus,  including  the  tonus  of  the  esoph- 
agus. The  increase  in  esophagus  tonus  causes  greater  pressure  on 
the  balloon,  and  in  consequence  stronger  mechanical  stimulation 
of  the  afferent  nerves  in  the  esophagus,  and  hence  the  rapid  or 
tetanic  contractions.  It  is  therefore  probable  that  the  actual  con- 
tractions of  the  esophagus  on  seeing  food  are  artifacts,  so  to  speak, 
due  to  the  presence  of  the  balloon. 

4.   THE  INTESTINES  IN  HUNGER 

Periods  of  active  contraction  of  the  small  intestines  in  hunger 
were  observed  in  the  duodenal  fistula  case  of  Busch.  Boldyreff 
found  that  the  intestines  (presumably  both  the  large  and  small 
intestine)  exhibit  rhythmic  contractions  during  the  periods  of  gas- 
tric hunger  contractions.  His  evidence  consisted  of  the  sounds 
produced  by  the  moving  gas  in  the  intestines  and  the  appearance 
of  the  free  end  of  the  fistula  of  the  small  intestine,  during  the 
periods  of  strong  rhythmical  contractions  of  the  empty  stomach. 
More  accurate  methods  of  registration  should  be  devised.  We 
have  observed  in  dogs  with  duodenal  fistula  evidences  of  contrac- 
tions in  the  duodenum  during  hunger  contractions  of  the  stomach 
(expulsion  of  bubbles  of  gas,  fluid,  debris,  etc.).  There  can  be  no 
doubt  that  Boldyreff's  observation  is  correct.  In  two  dogs  we 
introduced  balloons  both  into  the  stomach  and  into  the  large 
intestine  (descending  and  transverse  colon).  The  large  intestine 
showed  some  contractions,  but  these  were  not  correlated  with  the 
periods  of  gastric  hunger  contractions,  although  the  interesting 
theory  recently  developed  by  Alvarez  seems  to  imply  that  increased 
tonus  and  contractions  of  the  stomach  must  lead  to  increased 
motor  activity  in  the  entire  gut  below  the  stomach. 

Rumbling  intestinal  sounds  may  be  heard  when  the  stomach 
is  quiescent.  These  are  probably  due  to  local  stimulation  resulting 
from  distension  by  the  gases,  hence  mostly  confined  to  the  large 
intestine.  Rumbling  intestinal  sounds  are  usually  heard  during 
gastric  hunger  periods,  and  it  seems  to  us,  one  can  at  times  actually 


THE  STOMACH  IN  HUNGER  83 

feel  the  intestinal  movements.  If  this  is  the  case,  the  intestinal 
hunger  movements  must  be  much  more  vigorous  than  the  digestive 
movements.  The  character  of  the  intestinal  hunger  contractions 
is  not  known.  Do  they  consist  in  peristalsis,  in  segmentation,  or  in 
pendulum  movements  ?  Or  is  it  a  type  of  contraction  not  seen 
during  digestion:  rhythmic  contractions  and  relaxations  through- 
out the  whole  intestine  and  synchronous  with  the  systole  and 
diastole  of  the  hunger  beats  of  the  stomach  and  the  lower  end 
of  the  esophagus  ?  This  would  imply  a  type  of  co-ordination  of 
the  neuromuscular  mechanism  of  the  entire  digestive  tract  not 
revealed  by  the  movements  of  digestion.  In  the  movements  of 
digestion  the  esophagus,  the  cardia,  the  fundus,  antrum  pylori, 
the  pyloric  sphincter,  and  the  intestines  act  as  relatively  inde- 
pendent mechanisms  and  appear  to  be  governed  by  laws  of 
their  own  in  harmony  with  the  role  played  by  these  regions 
in  digestion. 

While  we  admit  the  possibility  that  the  contracting  esophagus 
and  intestines  may  contribute  to  the  sensation  of  hunger,  the  proof 
for  this  is  still  wanting,  and  in  any  event  the  stomach  is  the  main 
factor.  The  hunger  pangs  run  absolutely  parallel  with  the  periods 
of  gastric  hunger  contractions,  only  lagging  some  seconds  both  at 
the  beginning  and  the  end  of  each  contraction.  A  strong  contrac- 
tion artificially  induced  in  the  empty  stomach  is  recognized  as  a 
hunger  pang;  a  similar  contraction  induced  in  the  esophagus  when 
the  stomach  is  empty  is  recognized  as  something  quite  different 
from  hunger.  And  this  will  in  all  probabiHty  prove  to  be  true 
also  of  the  intestines.  No  one  can  fail  to  recognize  the  difference 
between  the  sensations  initiated  by  strong  contractions  in  the 
small  and  large  intestines  and  the  rectum  (intestinal  cramp,  tenes- 
mus, defecation)  and  the  gastric  hunger  pangs. 


CHAPTER  V 
SOME  ACCESSORY  PHENOMENA  OF  HUNGER 

Many  apparently  normal  persons  experience  in  hunger,  besides 
the  gnawing  pressure-pain  sensation  in  the  stomach,  a  feeling  of 
weakness,  "emptiness,"  headache,  and  sometimes  even  nausea.  A 
certain  degree  of  increased  excitabiHty  of  the  central  nervous  sys- 
tem, as  shown  by  restlessness,  irritability,  diminished  concentra- 
tion and  attention,  and  some  salivation  are  always  present  and 
must  be  looked  upon  as  a  necessary  efect  of  hunger  rather  than 
accessory  elements. 

We  call  these  states  or  symptoms  accessory  hunger  phenomena, 
because  they  are  not  always  present  in  hunger,  and  because  their 
relative  preponderance  depends  on  the  length  of  starvation  and  on 
some  individual  peculiarity  in  the  person.  It  must  be  admitted, 
however,  that  in  some  individuals  these  accessory  hunger  phe- 
nomena appear  to  overshadow,  if  not  entirely  to  suppress,  the 
pressure-pain  sensations  from  the  stomach.  This  is  probably  due 
to  a  relatively  unstable  condition  of  certain  central  nervous  mech- 
anisms rather  than  to  actual  absence  of  the  hunger  tonus  and 
hunger  contractions  of  the  empty  stomach,  although  there  are 
unquestionably  great  individual  variations  in  the  latter,  even  in 
comparatively  healthy  persons.  The  question  can  be  settled  by 
direct  test  on  persons  who  claim  to  feel  weakness  but  no  gastric 
hunger  pangs  in  starvation. 

We  think  most  observers  will  agree  that  in  the  normal  person 
the  hunger  experienced  4  to  lo  hours  after  a  meal  is  primarily  the 
gastric  gnawing  pangs,  with  practically  no  feeling  of  weakness, 
and  no  marked  or  obvious  hyperexcitability  of  the  brain  and  spinal 
cord.  This  is  the  justification  for  calling  the  gastric  sensation  the 
primary  and  essential  factor  in  the  hunger  complex.  Let  us  now 
consider  the  cause  of  the  accessory  hunger  phenomena,  and  their 
relation  to  the  gastric  hunger  pangs. 

84 


SOME  ACCESSORY  PHENOMENA  OF  HUNGER  85 

I.      GASTRIC   TONUS  AND  HUNGER  CONTRACTIONS   INCREASE 
REFLEX  EXCITABILITY  OF  CENTRAL  NERVOUS  SYSTEM 

This  is  readily  made  out  by  recording  the  ampHtude  of  the 
knee  jerk  (or  any  other  motor  reflex)  parallel  with  the  graphic 
recording  of  the  gastric  contractions.  Such  records  show  without 
exception  a  marked  increase  in  the  reflex  excitabihty  of  the  spinal 
cord  simultaneously  with  the  strong  hunger  contractions  of  the 
empty  stomach.'  The  reflex  excitability  usually  falls  to  normal 
level  during  the  pauses  between  the  single  contraction,  and  after 
the  strong  hunger  period  it  appears  to  be  somewhat  lower  than 
normal.  The  hunger  contractions  of  the  empty  stomach  frequently 
increase  the  reflex  response  of  the  cord  to  such  an  extent  that  a 
standard  minimal  stimulus  causes  a  maximal  response.  The  degree 
of  augmentation  of  the  reflex  is,  on  the  whole,  proportional  to  the 
ampHtude  of  the  stomach  contractions,  and  this  can  be  shown 
frequently  during  the  shortening  phase  of  a  single  contraction. 
There  are  many  exceptions  to  this  last  statement,  to  be  sure.  But 
this  is  to  be  expected  in  view  of  the  fact  that  under  conditions  as 
nearly  uniform  as  possible  two  successive  stimuli  of  equal  charac- 
ter and  intensity  rarely  give  two  successive  responses  of  equal 
magnitude. 

Some  attention  was  paid  to  the  question  whether  this  augmen- 
tation of  the  reflex  excitability  of  the  central  nervous  system 
synchronous  with  the  hunger  contractions  of  the  stomach  is  in 
evidence  before  the  contractions  have  given  rise  to  the  conscious 
hunger  pangs.  This  much  is  certain,  that  the  augmentation  is 
greatest  at  the  height  of  the  stomach  contraction  when  the  hunger 
pang  is  the  most  intense.  The  present  data  do  not  warrant  any 
statement  on  the  question  whether  or  not  the  beginning  of  the 
augmentation  precedes  the  conscious  hunger  pang  to  the  same 
extent  that  the  stomach  contraction  precedes  the  hunger  pang, 
because  little  importance  can  be  attached  to  slight  variations  in 
the  amplitude  of  the  reflex  response,  except  when  the  general 
average  is  made  significant  by  the  great  number  of  the  individual 
experiments.  The  stomach  contraction  is  the  primary  factor  or 
stimulus,  whether  or  not  conscious  cerebral  processes  constitute  a 


86 


CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 


II 


necessary  link  in  the  chain  of  events  that  results  in  augmentation 
of  the  reflexes. 

Lombard  concluded  from  experiments  on  himself  that  hunger 
depresses  the  knee  jerk.  No  account  is  given  of  the  degree  of 
hunger  experienced  by  him  before  lunch  and  dinner.    Possibly  he 


} L 


ittt(((ttt{tt(t{tttu(ttttttrtn -tmmtitnmmtnatttttttmtmtmttttmttmnmttnni 


Fig.  14. — I.  A,  record  of  the  knee  reflex;  B,  hunger  contractions  of  the  empty 
stomach;  showing  augmentation  of  the  knee  reflex  during  the  hunger  contractions. 
Time,  five  seconds.    About  one-half  original  size. 

II.  ^,  contractions  of  the  empty  stomach;  B,  plethysmograph  record  of  volume 
of  the  left  arm;  showing  a  vasomotor  rhythm  parallel  with  the  strong  hunger  con- 
tractions of  the  empty  stomach.    About  one-third  original  size. 

experienced  only  appetite  and  the  feeble  and  '^indefinite"  hunger 
that  may  be  present  in  the  absence  of  the  strong  stomach  con- 
tractions. In  such  conditions  there  is  no  augmentation  of  the  knee 
jerk  in  our  subject.  It  should  also  be  noted  that  in  some  cases 
Lombard  found  his  knee  reflex  greater  before  the  meal  (hunger  ?) 
than  after  the  meal. 


SOME  ACCESSORY  PHENOMENA  OF  HUNGER  87 

It  may  be  questioned  whether  a  comparison  of  the  amplitude 
of  the  knee  reflex  before  and  after  a  meal  is  an  adequate  criterion 
of  the  effect  of  hunger  states  on  the  reflex  excitabihty  of  the  spinal 
cord.  It  seems  to  us  that  this  is  a  comparison  between  hunger  (or 
appetite)  and  satiety,  and  not  between  hunger  and  the  absence  of 
hunger.  The  partaking  of  food  when  hungry  involves  many  changes 
of  a  positive  character  besides  the  aboHtion  of  hunger.  Hence  it 
is  clear  that  there  is  no  contradiction  between  our  results  and 
Lombard's  results  on  himself.  The  two  series  cannot  be  compared, 
because  the  conditions  of  the  subjects  were  not  comparable.  We 
have  made  no  tests  on  Mr.  V.  before  or  after  a  meal,  similar  to 
those  of  Lombard.  But  when  the  comparison  is  made  between  the 
state  of  hunger  (as  differentiated  from  appetite)  and  the  absence 
of  hunger,  the  evidence  is  conclusive  that  hunger  leads  to  or  is 
associated  with  an  increased  excitability  of  the  cerebro-spinal  axis. 
This  condition  probably  accounts  for  the  irritability,  restlessness, 
and  inability  to  maintain  a  fixed  attention — always  noted  in  con- 
nection with  strong  hunger,  and  in  some  persons,  even  in  case  of 
moderate  hunger.  The  afferent  nervous  impulses  from  the  stomach 
in  hunger  interfere  with  other  reflex  and  central  processes  by 
monopoly  of  attention  as  well  as  by  changes  in  the  reflex  centers. 
According  to  Weygandt  starving  persons  dream  more  than  usual 
in  their  sleep. 

Stimulation  of  the  gastric  mucosa  produces  a  similar  increase  in 
reflex  responses.  Thus  hot  or  cold  water,  introduced  into  a  stomach 
by  a  tube,  so  that  there  is  no  stimulation  of  the  nerves  in  the  mouth 
or  the  esophagus  invariably  augments  the  knee  jerk  in  man. 

Since  the  gastric  hunger  contractions  actually  induce  the 
increased  excitability  of  the  central  nervous  system  reflexly,  it 
follows  that  this  is  a  necessary  phenomenon  in  hunger.  The 
precise  degree  of  this  central  effect  will  depend  on  the  intensity 
of  the  hunger  contractions,  the  irritability  of  the  afferent  gastric 
nerves,  and  the  stability  of  the  central  organization.  The  increased 
reflex  excitability  and  restlessness  are,  at  least  in  part,  subconscious 
phenomena,  since  it  is  in  evidence  even  in  animals  deprived  of 
their  cerebrum  (Goltz,  Rogers). 


88  CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

II.      INFLUENCE   OF   GASTRIC  HUNGER   CONTRACTIONS   ON   THE 
HEART  AND   ON  THE  VASOMOTOR  MECHANISM 

1.  The  heart  heat. — During  the  period  of  strong  stomach  con- 
tractions the  rate  of  the  heart  beat  is  increased.  At  the  cessation 
of  the  contraction  period  the  heart  rate  becomes  slower  again. 
The  return  to  the  normal  rate  is  gradual.  If  the  motor  activities 
of  the  empty  stomach  are  very  vigorous,  so  that  the  pauses  between 
the  contraction  periods  are  relatively  short,  the  pulse  rate  may  not 
return  quite  to  the  normal  during  these  pauses.  The  average 
increase  in  the  rate  of  the  heart  beat  during  the  hunger  contractions 
of  the  stomach  is  eight  to  ten  beats  per  minute.  But  strong  indi- 
vidual contractions  or  tetanus  periods  may  show  an  increase  of 
thirty  beats  per  minute. 

When  the  details  of  the  contraction  periods  are  further  analyzed, 
it  is  found  that  the  greatest  acceleration  of  the  heart  beat  is  on  the 
whole  synchronous  with  the  individual  strong  contractions,  and 
that  the  pauses  between  the  contractions  usually  show  less  accel- 
eration. It  is  not  known  whether  this  effect  on  the  heart  is  a 
reflex  from  the  stomach,  or  due  to  a  direct  lowering  of  the 
vagus  tonus. 

2.  Vasomotor  changes  synchronous  with  the  contractions  of  the 
empty  stomach. — It  is  well  known  that  the  vasomotor  center  is 
acted  upon  not  only  by  practically  all  afferent  impulses,  but  also 
by  the  conscious  centrifugal  impulses  from  the  cerebrum.  None  of 
these  disturbing  factors  can  be  controlled  completely.  The  most 
we  can  do  is  to  endeavor  to  make  the  external  conditions  and  the 
cerebral  processes  as  uniform  as  possible.  This  was  attempted  in 
two  ways  during  these  experiments.  The  subject  was  permitted 
to  read  stories;  he  was  required  to  add  figures,  or  his  eyes  were 
covered  and  he  was  instructed  to  think  of  nothing  in  particular. 
Aside  from  the  varying  cerebral  states,  auditory  stimuli  are  the 
greatest  disturbing  factors. 

The  periods  of  strong  contractions  of  the  empty  stomach  are 
synchronous  with  great  variations  in  the  vasomotor  tone,  and  in 
most  cases  the  vasomotor  variations  exhibit  a  rhythm  similar  to 


SOME  ACCESSORY  PHENOMENA  OF  HUNGER  89 

that  of  the  stomach.  There  is  an  increase  in  volume  of  the  arm 
(vasodilation)  pari  passu  with  an  increasing  tonus  of  the  stomach 
and  with  the  beginning  of  the  individual  contractions,  but  the  arm 
begins  to  shrink  (vasoconstriction)  before  the  stomach  contraction 
has  reached  its  maximum.  Or  the  volume  of  the  arm  shows  a 
definite  increase  parallel  with  the  strong  contractions,  and  a  cor- 
responding diminution  in  the  arm  volume  during  the  stomach 
pauses.  These  two  types  of  vasomotor  rhythms  were  the  ones 
usually  obtained  during  periods  of  moderate  hunger  contractions. 
If  the  experiments  were  continued  for  long  periods  (4  to  6  hours), 
so  that  the  hunger  contractions  and  hunger  tetanus  became  very 
strong,  the  vasomotor  variations  were  in  evidence,  but  the  rhythms 
were  rarely  synchronous  with  the  stomach  rhythms.  In  such 
instances  the  subject  gave  unmistakable  signs  of  restlessness. 
Under  these  conditions  the  vasomotor  rhythm  may  be  slightly 
faster  or  slightly  slower  than  the  stomach  rhythm,  or  the  two 
rhythms  may  be  practically  identical,  but  the  contraction  phase 
of  the  stomach  activity  may  be  synchronous  with  a  decrease  in  the 
volume  of  the  arm  (vasoconstriction) . 

Before  the  appearance  of  the  first  period  of  hunger  contractions 
after  a  meal,  and  during  the  pause  or  relative  quiescence  of  the 
stomach  between  the  periods  of  moderate  hunger  contractions, 
another  type  of  vasomotor  rhythm  appears  in  the  plethysmographic 
records.  Considerable  attention  was  given  to  this  rhythm,  because 
the  rate  of  it  suggested  some  correlation  with  the  ''20-seconds 
rhythm  "  of  the  empty  stomach.  These  slight  variations  in  the  arm 
volume  are  frequently  irregular,  so  that  its  rate  cannot  be  made 
out  with  certainty,  but  when  the  fluctuations  are  fairly  regular 
the  rate  corresponds  closely  to  the  ^^20-seconds  rhythm"  of  the 
empty  stomach.  The  contraction  and  relaxation  phases  of  the  two 
rhythms  do  not  seem  to  correspond,  but  that  is  of  little  significance 
in  view  of  probable  difference  in  the  latent  time  of  the  respective 
neuro-muscular  apparatus  as  well  as  of  the  recording  devices. 
This  type  of  vasomotor  rhythm  is  most  marked  when  the  "20- 
seconds  rhythm"  of  the  stomach  is  the  strongest,  that  is,  at  the 
beginning  of  a  period  of  strong  hunger  contractions. 


90  CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

In  view  of  the  fact  that  the  vasomotor  center  is  acted  on  by 
so  many  factors,  central  and  peripheral,  the  parallelism  between 
the  vasomotor  tone  and  the  motor  activity  of  the  empty  stomach 
during  the  hunger  period  is  too  regular  to  be  accidental.  When 
the  synchrony  fails,  this  is  probably  due  to  central  or  peripheral 
factors  that  cannot  be  controlled  or  recorded.  The  question,  then, 
remains  how  this  synchrony  is  brought  about,  and  what  is  the 
biological  significance  of  it.  (i)  The  co-ordination  may  be  due  to 
associations  between  the  vasomotor  center  and  the  center  for  gas- 
tric tonus  in  the  medulla.  (2)  It  may  be  due  to  a  direct  action  on 
the  vasomotor  center  by  afferent  impulses  from  the  stomach 
initiated  by  the  stomach  contractions.  (3)  Or,  it  may  be  due  to  the 
influence  on  the  vasomotor  center  of  the  conscious  processes  of 
hunger,  which  are  caused  by  the  stomach  contractions.  Brodie 
and  Russel,  and  Miller  have  studied  the  effect  on  the  blood  pres- 
sure of  stimulation  of  the  central  end  of  the  gastric  branches  of 
the  vagi  in  animals  under  general  anesthesia.  The  changes  in  the 
blood  pressure  are  variable  and  compHcated  by  respiratory  changes 
and  vomiting  movements.  In  dogs  and  cats  the  primary  effects 
may  be  either  an  increase  or  a  decrease  in  the  arterial  pressure,  while 
in  rabbits  the  stimulation  seems  to  cause  a  rise  in  the  blood  pres- 
sure only.  It  will  probably  be  difficult  to  secure  experimentally 
the  selective  stimulation  of  the  afferent  gastric  nerve  fibers  that 
are  stimulated  by  the  contraction  of  the  empty  stomach.  There 
may  be  some  connection  between  the  vasomotor  rhythms  described 
above  and  the  well-known  Traube-Hering  blood-pressure  variations, 
as  the  latter  are  frequently  induced  by  experimental  interferences 
with  the  vagi. 

III.      SALIVATION 

When  a  suitable  cannula  is  put  in  the  Stenson's  duct  in  man 
so  that  the  rate  of  flow  of  the  saliva  can  be  measured  accurately, 
and  with  a  balloon  in  the  stomach  to  register  the  gastric  hunger 
contractions,  one  can  demonstrate  that  there  is  a  rhythm  of  the 
salivary  flow  parallel  to  the  gastric  hunger-contraction  rhythm. 
Each  strong  hunger  contraction  is  accompanied  by  a  brief  gush  of 


SOME  ACCESSORY  PHENOMENA  OF  HUNGER  91 

saliva  from  the  duct.  The  amount  of  salivation  varies  with  the 
individual  person,  and  it  varies  somewhat  from  day  to  day  in  the 
same  individual.  The  feebler  contractions  have  no  evident  effect 
on  the  saliva  flow.  This  saliva  flow  is  independent  of  the  memory, 
sight,  or  smell  of  palatable  food  during  the  hunger,  but  it  is  certain 
that  these  stimuli  and  the  central  processes  induced  by  them  will 
augment  the  salivation. 

The  increased  flow  of  saliva  that  occurs  simultaneously  with 
the  strong  hunger  contractions  is  probably  a  reflex  effect  from 
stimulation  of  sensory  nerves  in  the  stomach  by  the  contractions. 
It  is  well  known  that  strong  stimulation  of  gastric  nerves  induces 
salivation  and  vomiting.  Such  stimulation  is  usually  held  to  act 
on  the  nerves  in  the  mucosa,  while  the  stomach  contractions 
stimulate  the  nerves  in  the  muscularis  mainly.  It  is  probable 
that  strong  stimulation  of  the  sensory  nerves  in  the  sub-mucosa 
and  in  the  muscular  layers  also  causes  reflex  salivation. 

Some  increased  salivation  is  therefore  a  necessary  effect  of 
strong  hunger,  irrespective  of  the  presence  of  appetite,  or  the 
memory,  sight,  or  smell  of  good  food.  But  the  more  copious 
^'watering  of  the  mouth"  that  accompanies  the  thought  or  sight 
of  appetizing  food  is  not  of  gastric  origin. 

IV.     EFFECTS   ON  THE  VASOMOTOR  CENTER  OF  STIMULATION  OF 
THE  GASTRIC  MUCOSA 

When  cold  or  hot  water  is  introduced  into  the  stomach  through 
the  tubes  in  quantities  of  50  to  100  c.c.  at  a  time,  there  is  nearly 
always  a  shrinking  of  the  arm,  that  is,  vasoconstriction.  Water 
at  body  temperature  does  not  seem  to  affect  the  tonus  of  the  vaso- 
motor center.  Water  at  10°  C.  causes  less  vasoconstriction  than 
water  at  55°  C. 

In  order  to  ascertain  whether  this  reflex  is  due  to  the  influence 
on  the  vasomotor  center  by  conscious  processes,  similar  experi- 
ments were  performed  while  the  subject  was  asleep.  It  is  not  an 
easy  matter  to  go  to  sleep  with  a  plethysmograph  on  one  arm  and 
two  rubber  tubes  in  one's  throat  and  esophagus.  But,  after  marked 
physical  fatigue  it  is  possible.    The  same  rhythmic  variation  in  the 


92  CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

vasomotor  tone  is  observed  as  before,  but  perfectly  relaxed.  There 
is  a  gradual  increase  in  the  size  of  the  arm  as  the  tonus  of  the 
stomach  increases.  This  increase  or  vasodilation  is  greatest  when 
the  stomach  contractions  are  highest  and  the  size  of  the  arm  de- 
creases as  the  stomach  relaxes.  From  this  it  seems  evident  that 
this  activity  of  the  vasomotor  center  is  not  due  to  conscious 
processes. 

Moderately  hot  or  moderately  cold  water  in  the  stomach  does 
not  seem  to  affect  the  activity  of  the  vasomotor  center  during 
sleep.  Very  cold  water  either  does  not  have  any  very  marked  effect, 
or  else  the  stimulation  is  sufficient  to  awaken  the  subject.  Warm 
water  did  not  cause  a  marked  vasoconstriction  unless  the  subject 
woke  up  as  a  result  of  the  injection.  The  marked  vasoconstriction 
observed  when  the  stomach  mucosa  is  stimulated  with  very  cold  or 
very  warm  water,  therefore,  seems  to  be  due  mainly  to  the  effect 
of  conscious  processes  on  the  vasomotor  center. 

v.      FEELINGS   OF   WEAKNESS,   " EMPTINESS,"   HEADACHE,   AND 
NAUSEA  IN  HUNGER 

I.  The  weakness  accompanying  hunger  is  evidently  of  complex 
origin,  or  partly  due  to  sensory  impulses  from  the  digestive  tract, 
and  partly  to  relative  exhaustion  in  the  tissues.  Voit  thought 
that  the  feeling  of  weakness  is  a  general  sensation  in  some  way 
caused  by  lack  of  nutrient  materials  in  the  blood.  That  in  moderate 
hunger  only  the  first  or  reflex  factor  is  involved  is  evident  from  the 
fact  that  this  weakness  is  abolished  by  taking  food  into  the  stomach, 
before  there  is  any  digestion  and  absorption  of  the  food  material 
into  the  blood.  After  several  days  of  starvation,  the  feeling  of 
weakness  does  not  all  disappear  immediately  following  a  meal. 
Hence  we  must  here  be  dealing  also  with  the  factor  of  replenishing 
the  tissues.  How  does  the  hunger  state  of  the  stomach  and  intes- 
tines induce  the  feeling  of  weakness  ?  We  have  seen  that  this 
hunger  state  means  strong  tonus  and  contractions  of  the  empty 
stomach  and  intestines.  It  probably  also  involves  a  greater  degree 
of  tonus  of  the  abdominal  muscles  in  the  maintenance  of  the  intra- 
abdominal pressure.    It  is  not  clear,  however,  why  tonus  and 


SOME  ACCESSORY  PHENOMENA  OF  HUNGER  93 

contractions  in  the  empty  stomach  should  in  some  people  pro- 
duce the  feeling  of  weakness. 

We  are  not  convinced  that  the  vasomotor  disturbances  caused 
by  the  hunger  contractions  are  great  enough  to  produce  the  feeling 
of  weakness.  There  are  probably  other  reflex  factors  at  present 
unknown.  At  the  same  time,  the  degree  of  weakness  caused  by 
identical  peripheral  factors  evidently  depends  on  the  stability 
of  the  central  nervous  organization,  for  in  disease  (hysteria, 
neurasthenia,  etc.)  a  degree  of  hunger  which,  in  a  normal  person, 
would  not  induce  the  feeling  of  weakness  may  cause  extreme 
prostration. 

2.  The  feeling  of  ^^ emptiness.'^ — Strong  sensation  of  hunger  is 
usually  accompanied  by  a  peculiar  feeling  of  *' emptiness"  in  the 
entire  abdominal  region.  This  feeling  is  continuous,  not  inter- 
mittent like  the  pangs  of  hunger.  The  ^'emptiness"  feeling  does 
not  disappear  entirely  during  the  relative  quiescences  of  the  empty 
stomach  between  the  hunger  periods. 

This  feeling  is  probably  more  complex  in  its  origin  than  the 
hunger  pangs.  It  is  well  known  that  a  very  complete  evacuation 
of  the  large  intestines,  as  by  enemas  or  purgatives,  induces  a  feeling 
of  emptiness.  The  feeling  may  be  partly  abolished  by  moderate 
but  steady  pressure  on  the  abdominal  wall.  It  is  probable  that 
the  increased  tonus  of  the  abdominal  muscles,  in  consequence  of 
the  empty  state  of  stomach  and  intestines,  contributes  to  the  feel- 
ing in  some  way.  It  is  well  known  that  the  intra-abdominal  pres- 
sure remains  nearly  constant  under  varying  degrees  of  fulness  and 
emptiness  of  the  digestive  tract. 

Since  in  starvation  there  is  persistent  hypertonus  of  the 
abdominal  muscles,  we  question  whether  any  part  of  the  feeling 
of  emptiness  originates  in  the  stomach  itself.  It  is  not  so  difficult 
to  understand  how  a  hypertonic  and  rhythmically  contracting 
empty  stomach  may  give  rise  to  sensations  of  tension,  pressure, 
and  gnawing  pain.  But  how  can  it  cause  the  sensation  of  empti- 
ness, unless  this  feeling  is  merely  the  negative  of  the  sensation  of 
fulness  ?  On  the  other  hand,  if  the  tonus  of  the  abdominal  muscles 
does  not  suffice  to  maintain  the  normal  intra-abdominal  pressure 


94  CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

when  stomach  and  intestines  are  relatively  empty  and  strongly 
contracted  in  hunger,  the  tension  on  all  the  visceral  organs  would 
be  diminished,  and  this  in  turn  would  alter  the  pressure  relation 
to  the  peritoneum  and  the  mesentery.  If  this  is  a  factor  in  the 
origin  of  the  feeling  of  abdominal  '' emptiness"  in  hunger,  the 
sensation  should  be  diminished  in  man  by  lying  down,  in  compari- 
son with  that  felt  when  standing.  The  writer  cannot  test  this 
hypothesis  on  himself,  as  the  feeling  of  "emptiness"  is  not  a 
prominent  part  of  his  hunger  complex. 

3.  Headache  and  nausea. — The  author  experiences  sHght  head- 
ache and  a  suggestion  of  nausea  only  after  4  or  5  days'  starvation, 
but  there  is  no  doubt  that  a  few  apparently  normal  people  experi- 
ence both,  or  more  particularly  the  headache,  during  the  moderate 
hunger  that  comes  on  4  to  6  hours  after  eating.  Some  of  Boring's 
subjects  had  difficulty  in  distinguishing  between  hunger  and  nausea 
in  their  own  consciousness.  In  such  cases  there  can  be  no  starva- 
tion change  in  the  blood  and  tissues.  And  the  fact  that  headache 
as  well  as  nausea  is  greatly  relieved  at  once  by  taking  food  into 
the  stomach  seems  to  show  that  they  are  essentially  of  gastric  or 
reflex  origin.  It  is  well  known  that  both  headache  and  nausea 
can  be  produced  by  disturbances  in  circulation,  and  that  nausea 
can  be  caused  by  stimulation  of  nerves  in  the  stomach  mucosa 
(normal  stimulation  of  hyperexcitable  nerves,  or  excessive  irrita- 
tion of  the  normal  nerves) .  Possibly  the  strong  hunger  contractions 
of  the  empty  stomach  cause  sufficient  stimulation  of  the  gastric 
nerves  to  induce  both  headache  and  nausea  in  certain  individuals. 
This  can  be  determined  experimentally  on  such  persons.  Unfor- 
tunately, the  author  does  not  himself  experience  these  accessory 
hunger  phenomena,  nor  has  he  been  able  to  secure  as  subject  a 
person  with  these  hunger  symptoms  sufficiently  marked  to  make 
it  worth  while  investigating.  In  prolonged  starvation  there  is 
a  contributory  factor,  namely,  a  greater  degree  of  increased 
excitability  both  of  the  gastric  nerves  and  of  the  central  nervous 
system. 

So  far  as  established  facts  permit  conclusions  or  point  the  way, 
the  accessory  hunger  phenomena,  excepting  the  exhaustion  fatigue 


SOME  ACCESSORY  PHENOMENA  OF  HUNGER  95 

of  prolonged  starvation,  are  caused  reflexly  by  the  hunger  tonus 
and  the  hunger  contractions  of  the  empty  stomach.  The  degree 
with  which  they  are  manifested  in  hunger  depends  on  the  intensity 
of  the  hunger  contractions,  the  excitabiHty  of  the  sensory  nerves 
of  the  stomach,  and  on  the  relative  stability  of  the  central  nervous 
organization  of  the  individual  person. 


CHAPTER  VI 

THE  RELATION  OF  HUNGER  TO  APPETITE 

Physiologists,  psychologists,  and  clinicians  who  have  devoted 
no  special  attention  to  the  nature  of  hunger  and  appetite  appear 
to  accept  the  common  view  of  the  laity  that  the  two  sensations  are 
the  same  in  quality,  and  differ  only  in  intensity.  Thus  mild  hunger 
is  called  appetite,  while  strong  appetite  is  called  hunger.  If  the 
two  sensation  complexes  are  in  a  linear  series  and  thus  involve 
identical  mechanisms,  either  the  term  appetite  or  the  term  hunger 
is  superfluous,  and  it  would  be  more  correct  and  less  confusing  to 
speak  of  mild  and  strong  appetite  or  mild  and  strong  hunger.  We 
do  not  apply  different  terms  to  the  sensation  of  sweetness  or  of 
red  according  to  the  intensity  of  the  sweet  sensation  or  the  satura- 
tion of  the  red  color.  A  sensation  remaining  identical  in  quality 
but  differing  in  intensity  should  have  only  one  name,  and  the 
intensity  variation  should  be  denoted  by  the  usual  adjectives. 

Most  authors  who  have  given  some  special  attention  to  hunger 
and  appetite  take  the  position  that  the  two  sensations  are  funda- 
mentally different,  that  is,  that  they  differ  in  quality.  This  view 
is  supported  by  Albu,  Boas,  Boring,  Cannon,  Carlson,  Krehl, 
Nicolai,  Roux,  Sternberg,  Stiller,  and  many  others.  Stiller  thinks 
that  appetite  is  the  sensation  of  hunger  plus  the  memories  of  taste 
and  smell  of  foods;  hence  one  may  experience  hunger  without 
appetite,  but  not  appetite  without  hunger.  But  others  maintain 
that  one  may  also  experience  appetite  without  the  sensation  of 
hunger,  as  in  the  case  of  eating  palatable  desserts  at  the  end  of  a 
full  and  satisfying  meal. 

Practically  all  writers  who  have  recognized  the  quaHtative 
difference  between  hunger  and  appetite  state  that  hunger  is  pri- 
marily an  unpleasant  and  painful  sensation  and  more  or  less  inter- 
mittent, while  appetite  is  essentially  pleasant  in  character  and 
without  definite  periodicity.     Hunger,  again,  is  referred  to  the 

96 


THE  RELATION  OF  HUNGER  TO  APPETITE  97 

stomach,  while  the  appetite  complex  is  referred  to  the  mouth 
and  throat. 

We  have  seen  that  hunger  is  an  uncomfortable  pain  sensation 
caused  by  stomach  contractions.  Is  appetite  also  a  sensation,  or 
is  it  essentially  a  memory  process  ?  If  appetite  is  or  contains  imme- 
diate sensory  elements,  what  mechanisms  in  the  mouth  and  throat 
initiate  the  sensory  impulses  ?  In  one  of  his  earHer  papers  Stern- 
berg suggested  that  appetite  is  in  some  way  associated  with  the 
tonus  of  the  muscles  of  mastication  and  deglutition;  and  that 
absence  of  appetite,  that  is,  nausea,  is  due  to  atony  of  these  muscles. 
Later  Sternberg  suggested  that  appetite  is  caused  by  peristalsis  of 
the  esophagus  and  stomach,  while  lack  of  appetite  is  due  to  anti- 
peristalsis  in  these  organs.  This  appears  to  us  a  very  superficial 
suggestion.  It  is  logical,  to  be  sure,  but  it  is  contrary  to  fact.  In 
the  very  full  stomach  there  is  active  peristalsis,  but  that  does 
not  necessarily  cause  appetite.  And  there  is  no  peristalsis  in 
the  esophagus  except  that  induced  by  swallowing.  If  esophageal 
and  gastric  peristalsis  are  the  stimuli  that  initiate  appetite, 
this  sensation  should  show  a  rhythmicity  similar  to  that  of 
hunger. 

Sternberg,  and  after  him  Vorkastner,  and  others  are  guilty  of 
a  singular  misrepresentation  of  Pavlov's  conception  of  appetite. 
These  German  writers  charge  Pavlov  with  saying  that  "Appetit 
ist  saft" — appetite  is  gastric  juice.  We  cannot  find  any  such 
statement  in  Pavlov's  work,  and  the  view  is  obviously  inconsistent 
with  the  whole  trend  of  his  research  on  the  work  of  the  digestive 
glands.  Pavlov  has  shown  that  appetite  is  a  necessary  condition 
for  the  secretion  of  appetite  gastric  juice,  but  appetite  by  itself 
does  not  induce  the  secretion,  nor  does  the  gastric  juice  by  itself 
induce  appetite,  although  it  may  contribute  to  it  by  gentle  stimu- 
lation of  the  gastric  mucosa. 

According  to  Cannon,  *' appetite  is  related  to  previous  sensa- 
tions of  the  taste  and  smell  of  food.  These  sensory  associations 
determine  the  appetite  for  any  edible  substance,  and  either  this 
memory  or  present  stimulation  can  arouse  the  desira."  In  brief, 
appetite  is  caused  either  by  the  immediate  taste  and  smell  of 


98  CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

palatable  food,  or  induced  by  the  memory  processes  of  such  taste 
and  smell  sensations. 

Some  of  Boring's  subjects  described  ''a  kines thesis  in  the  throat 
and  oral  sensation  arising  from  the  free  flow  of  saliva,  a  complex 
which  to  them  meant  desire  for  food.  Here  we  have  a  true  sensory 
basis  of  appetite.  The  ideation  of  food  is  no  doubt  a  usual  con- 
comitant, and  presumably  it  often  constitutes  a  desire  for  food 
that  lacks  sensory  components  entirely."  Boring  thus  includes  in 
appetite  the  sensations  aroused  by  increased  saHvation,  and  pos- 
sibly from  increased  tonus  in  the  muscles  of  mastication  and  deglu- 
tition, but  not  the  taste  and  smell  sensations,  to  which  Cannon 
gives  such  a  prominent  position.  It  may  be  noted,  however,  that 
salivation  or  increased  tonus  either  singly  or  combined  do  not  by 
themselves  induce  the  sensation  of  appetite. 

The  delineation  of  the  appetite  complex  and  its  relation  to 
hunger  is  a  question  of  analysis  of  one's  own  sensation  under  such 
experimental  control  as  can  be  applied.  Now,  it  is  obvious  that 
neither  the  sight,  the  taste,  nor  the  smell  of  good  food,  the  memory 
of  these  sensations,  or  salivation  and  throat  kines thesis  can  by 
themselves  invariably  induce  appetite.  We  all  know  that  the 
taste  or  smell  of  the  best  of  food  in  the  case  of  severe  gastritis 
induces,  not  appetite,  but  nausea.  Salivation  induced  by  a  drop 
of  vinegar  in  the  mouth  does  not  cause  appetite.  And  in  nervous 
anorexia  all  of  the  immediate  stimuli  and  the  memory  processes 
mentioned  by  Cannon  and  Boring  may  be  present  or  called  forth 
without  producing  a  desire  for  food.  It  is  thus  clear  that  a  certain 
sensation  complex  from  the  viscera  and  an  approximately  normal 
state  of  central  correlations  constitute  a  necessary  background  for 
the  development  of  appetite.  Given  this  background,  the  central 
and  essential  element  in  appetite  is  the  memory  processes  of  past 
experience  (sight,  smell,  taste)  with  palatable  foods.  These  memo- 
ries are  reinforced  by  present  stimulation  of  these  nerves  by  the 
food,  since  everyone  knows  that  appetite,  unless  intense  at  the 
outset,  is  increased  by  the  very  act  of  eating. 

It  will  be  shown  that  part  of  this  augmentation  is  due  to  chemical 
stimulation  of  the  nerves  in  the  gastric  mucosa.    The  mouth  and 


THE  RELATION  OF  HUNGER  TO  APPETITE  99 

throat  kinesthesis  and  the  sensation  due  to  salivation  are,  in  the 
author's  judgment,  accessory  elements  in  appetite  analogous  to 
the  sensations  of  weakness  and  emptiness  in  hunger. 

But  how  can  we  account  for  the  desire  for  food  that  seems  to 
be  inherent  in  the  appetite  elements  ?  We  have  suggested  elsewhere 
that  this  urge  may  be  an  inherited  (partly  subconscious)  factor 
(positive  chemotropism),  fusing  with  the  memory  processes  of  taste 
and  smell  of  foods  as  soon  as  these  become  a  part  of  the  individual's 
experience.  It  seems  that  this  urge  is  present  in  appetite  even  when 
there  is  no  call  for  food  on  the  part  of  the  empty  stomach;  hence  it 
is  not  a  vague  hunger.  Pleasant  sensations  of  different  kinds,  such 
as  are  induced  by  works  of  art,  music,  or  the  beauties  of  nature  do 
not  seem  to  contain  or  arouse  analogous  desires.  In  the  author's 
experience  the  fragrance  of  the  rose  in  the  garden  is  as  pleasing 
as  the  fragrance  of  the  roast  in  the  kitchen,  but  the  desire  to  enjoy  ^ 
the  former  cannot  be  compared  with  the  urge  to  ingest  the  latter. 

It  seems  to  us  that  the  old  view  that  hunger  and  appetite  are 
different  intensities  on  the  same  sensation  curve  is  no  longer  tenable 
even  as  a  theory.  The  conception  came  about  through  lack  or 
difficulty  of  analysis  of  all  factors  involved,  and  the  tendency  to 
fuse  or  confuse  in  consciousness  heterogeneous  sensations  that  are 
usually  aroused  simultaneously,  as  is  the  case  with  the  taste  and 
smell  of  food.  In  the  normal  individual  hunger  and  appetite  are 
usually  experienced  simultaneously.  If  only  vague  or  mild  hunger 
is  present,  the  appetite  elements  occupy  the  high  seat  in  conscious- 
ness; when  hunger  becomes  markedly  painful,  attention  is  focused 
on  this  element.  If  we  start  to  masticate  palatable  food  or  by 
means  of  a  stomach  tube  put  a  Hquid  or  Hquid  food  directly  into  the 
stomach  at  the  height  of  a  period  of  gastric  hunger  contractions, 
the  latter  are  inhibited  at  once  and  the  unpleasant  hunger  sensa- 
tion disappears  at  the  same  time,  while  the  pleasant  appetite 
complex  is  initiated  or  intensified.  In  this  way  we  institute  a 
successive  contrast  between  hunger  and  appetite,  so  that  they  can 
be  compared  with  greater  accuracy. 

In  everyday  Hfe  of  adult  persons  having  access  to  a  Hberal  food 
supply  the  memory  elements  of  appetite  are  probably  a  greater 


lOO        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

factor  in  the  ingestion  and  digestion  of  food  than  hunger,  as  short 
intervals  between  large  meals  do  not  permit  the  development  of 
strong  hunger  unless  the  individual  is  engaged  in  hard  physical 
work.  Under  these  circumstances  appetite  and  habit  supplant 
hunger  as  nature's  dietary  guide.  Everyone  knows  that  if  the 
food  is  made  sufficiently  palatable  we  may  consume  large  quantities 
of  it  without  being  hungry  or  actually  needing  the  food,  especially 
if  one  has  formed  the  habit  of  giving  marked  attention  to  the 
pleasures  of  the  table. 


CHAPTER  VII 
THE  SENSIBILITY  OF  THE  GASTRIC  MUCOSA 

The  active  controversy  concerning  the  sensibiHty  of  the  visceral 
organs  that  has  been  going  on  since  the  time  of  Haller  is  essentially 
a  question  to  what  extent  afferent  nervous  impulses  from  the  viscera 
influence  conscious  processes.  Haller  thought  the  visceral  organs 
were  insensitive,  especially  to  pain.  Afferent  or  sensory  nerve- 
fibers  are  distributed  to  all  the  internal  organs.  But  the  stimula- 
tion of  these  nerves  may  produce  local  reflexes  only,  or  central 
reflexes  of  subconscious  character  (tonus,  vascular,  respiratory, 
etc.).  Lennander,  a  surgeon,  observing  numerous  patients  in 
abdominal  operations,  under  local  anesthesia  for  the  abdominal 
wall,  reached  the  conclusion  that,  excepting  the  parietal  peritoneum, 
the  entire  viscera  (stomach  included)  is  insensitive,  especially  to 
pain.  If  Lennander's  view  is  correct  the  hunger  pains  cannot  be 
of  gastric  origin.  We  presume  Lennander  would  ascribe  them  to 
mechanical  tension  or  pressure  on  the  parietal  peritoneum  from 
the  strong  contractions  of  the  empty  stomach.  Lennander's  assist- 
ant, Nystrom,  and  MacKenzie,  Becher,  and  Mitchell  have  accepted 
and  attempted  still  further  to  substantiate  and  defend  this  radical 
theory.  But  other  workers  have  shown  that  it  is  untenable.  Kast 
and  Meltzer  obtained  distinct  evidence  of  pain  on  injury  or  strong 
stimulation  of  the  viscera,  and  showed,  moreover,  that  local  anes- 
thetics (subcutaneous  injection  of  cocaine)  tend  to  depress  visceral 
sensibility.  Kast  and  Meltzer,  and  Ritter  suggest  that  this  accounts 
for  Lennander's  erroneous  conclusion,  as  local  anesthesia  was  used 
in  practically  all  his  patients.  New  experimental  facts  as  well  as 
critical  considerations  demonstrating  certain  sensibiUties  of  all  the 
visceral  organs  have  also  been  published  by  Neumann,  Hertz, 
Head,  Rivers  and  Sherran,  Boring,  and  others.  But  in  the  present 
work  we  are  .'concerned  with  the  sensibiUty  of  the  alimentary  canal, 
and  especially  that  of  the  stomach. 


i02        tONTKOL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

I.      ABSENCE   OF  PAIN   SENSATION  FROM   THE   NORMAL 
GASTRIC  MUCOSA 

The  sensation  of  pain  cannot  be  produced  from  the  normal 
gastric  mucosa  except  by  stimuli  that  evidently  cause  some  destruc- 
tion of  cells  and  nerve-endings,  such  as  strong  acids,  oil  of  mustard, 
absolute  alcohol,  excessive  heat,  etc.  The  normal  mucosa  can  be 
pressed  or  squeezed  with  forceps  until  crushed,  pins  may  be  pushed 
into  the  mucosa  anywhere,  or  the  mucosa  may  be  incised  with  a 
scalpel,  without  causing  pain  in  a  normal  person.  The  gastric 
pain  caused  by  strong  and  destructive  chemicals  acting  on  the 
normal  mucosa  may  be  due  to  over-stimulation  of  nerve-fibers 
other  than  those  of  ''protopathic"  pain.  In  the  case  of  a  hyper- 
excitable  stomach  mucosa,  as  in  certain  types  of  gastritis,  sub- 
stances normal  to  the  stomach  cavity  (water,  gastric  juice)  may 
cause  pain.  Strong  tonus  and  contraction  of  the  stomach  are 
painful,  and  it  is  not  certain  that  the  kinesthetic  pain  from  gastric 
contraction  is  excluded  in  all  cases  of  pain  from  destructive  chemical 
stimulation  of  the  normal  mucosa,  or  normal  stimulation  of  the 
hypersensitive  mucosa,  since  the  motor  conditions  of  the  stomach 
in  these  states  have  not  been  studied  sufficiently.  Hertz  supports 
the  view  that  all  so-called  gastric  pains,  even  those  induced  by 
destructive  chemical  stimulation  of  the  mucosa,  are  due  to  exces- 
sive contractions  of  the  pylorus  and  the  pyloric  end  of  the  stomach. 
There  can  be  little  doubt  that  strong  acids  on  reaching  the  duode- 
num will  cau^e  temporary  spasms  or  tetany  of  the  upper  part  of 
the  duodenum,  and  probably  of  the  pylorus.  The  precise  genesis 
of  these  pains  must  still  be  considered  an  open  question.  In  our 
own  experience  these  pains  are  too  persistent  to  be  due  to  peristalsis. 
It  they  are  of  purely  muscular  origin,  the  stomach  and  duodenal 
contractions  giving  rise  to  them  must  be  prolonged  tonus  or  tetany 
contractions.  It  is  probable  that  the  pain  is  essentially  muscular, 
but  the  injured  mucosa  may  also  be  a  factor. 

Excessive  distension  of  the  stomach  by  food,  water,  gas,  or 
inflated  balloons  causes  pain  referred  to  the  stomach,  but  there  is 
no  evidence  that  this  pain  is  due  to  stimulation  o^  the  mucosa 
nerves. 


THE  SENSIBILITY  OF  THE  GASTRIC  MUCOSA  103 

We  are  thus  forced  to  the  conclusion  that  the  only  physiological 
pains  from  the  stomach  are  the  pangs  of  hunger,  and  these  do  not 
arise  from  the  mucosa  nerves.  All  pains  possibly  originating  in  the 
mucosa  are  indices  of  pathological  processes,  that  is,  either  destruc- 
tive stimuli  acting  on  the  normal  nerve,  or  normal  stimuli  action 
on  hyperexci table  nerves.  These  gastric  pains  will  be  considered 
in  greater  detail  in  the  chapter  on  hunger  and  appetite  in  disease 
(chap.  xvi). 

II.      THE  ABSENCE   OF   TRUE   TACTILE   SENSIBILITY 

Everyday  experience  tells  us  the  stomach  mucosa  is  not  sensitive 
to  touch.  Pavlov  states:  ''It  can  hardly  be  doubted  that  under 
normal  conditions  the  surface  of  the  stomach  has  a  certain  degree 
of  tactile  sensibility."  The  term  tactile  sensibiHty  is  evidently  used 
here  in  the  sense  of  a  general  response  to  mechanical  stimulation 
rather  than  as  implying  a  true  tactile  sensibiHty.  When  solid  food 
is  swallowed,  no  tactile  sensation  is  felt  after  the  food  has  passed 
the  pharynx,  unless  the  mass  is  so  large  that  it  causes  unusual 
distension  of  the  esophagus.  In  that  case  it  may  be  felt  all  the 
way  down  the  esophagus,  but  this  is  due  to  the  distension  of  the 
wall  of  the  esophagus  and  is  not  a  tactile  sensation  from  contact 
with  the  mucosa. 

Hertz  tested  on  himself  the  tactile  sensibility  of  the  mucosa  of 
the  esophagus' by  means  of  an  esophagoscope  with  a  slit  down  the 
side,  so  that  a  metal  bulb  in  a  long  holder  could  be  moved  along 
the  mucous  membrane  of  the  esophagus  and  the  pharynx.  The 
pharyngeal  mucosa  was  found  to  be  sensitive  to  touch;  the  esoph- 
ageal was  insensitive. 

The  author  has  tested  the  tactile  sensibiHty  of  his  own  gastric 
mucosa,  swallowing  a  good-sized  rubber  tube,  through  which  was 
passed  a  test-tube  brush  attached  to  a  strong  piano  wire.  PulHng 
the  test-tube  brush  about  in  the  cavity  of  the  stomach  produced 
no  sensation. 

Numerous  tests  were  made  on  the  gastric  mucosa  of  Mr.  V., 
our  gastric  fistula  case.  Gently  touching  or  striking  the  mucosa 
with  blunt  objects  produced  no  sensation.    If  the  mucosa  is  rubbed 


I04        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

or  pressed  very  vigorously  with  a  blunt  object  Mr.  V.  says  he  ''can 
feel  it";  he  cannot  describe  the  sensation  thus  produced  except 
in  a  negative  way.  It  is  not  like  touch,  nor  is  it  pain  or  hunger. 
Whatever  the  character  of  the  sensation  may  be,  we  are  satisfied 
that  it  is  a  real  change  in  the  stream  of  consciousness,  for  he  recog- 
nizes these  stimuli  when  he  has  no  other  means  of  knowing  that 
the  gastric  mucosa  is  being  handled.  The  sensation  may  not  orig- 
inate in  the  mucosa,  but  in  the  muscularis  (tonus  relaxation  through 
reflex  inhibition)  or  possibly  in  the  visgeral  peritoneum,  as  the 
pressure  must  be  considerable  to  produce  it.  We  are  satisfied  that 
the  stimulation  of  the  normal  gastric  mucosa  of  Mr.  V.  does  not 
produce  tactile  sensation.  The  same  conclusion  has  been  reached 
by  previous  workers  using  human  gastric  fistula  cases. 

III.      GASTRIC   TEMPERATURE   SENSATIONS 

In  1846  Weber  suggested  that  the  sensation  of  cold  or  warmth  in 
the  epigastrium,  after  drinking  ice-cold  or  very  warm  water, 
originates  in  the  skin  of  the  abdomen  over  the  stomach  and  not  in 
the  stomach  mucosa.  According  to  Weber  sufiicient  conduction 
takes  place  through  the  walls  of  the  stomach  and  abdomen  to 
stimulate  the  temperature  nerves  of  the  skin.  Becher  swallowed 
a  single  rubber  tube  and  through  it  injected  water  of  different 
temperatures  into  the  stomach.  He  did  not  experience  any  heat 
or  cold  sensation  before  the  heat  or  cold  had  passed  through  the 
walls  of  the  tube  and  stimulated  the  mucosa  of  the  esophagus. 
Mueller  concluded  that  ice  water  produced  no  sensation  in  the 
stomach.  Zimmerman  irrigated  his  stomach  with  hot  or  cold 
water  through  a  thick  rubber  tube.  He  claims  that  hot  or  cold 
sensations  were  felt  only  when  the  lower  end  of  the  tube  was  30 
to  25  cm.  distant — hence  not  far  from  the  lower  end  of  the  esopha- 
gus. He  therefore  concludes  that  the  sensation  is  projected  from 
the  esophageal  mucosa.  MacKenzie  beheves  that  the  temperature 
sensations  induced  by  hot  and  cold  water  entering  the  stomach  is 
due  to  reflex  vasomotor  changes  in  the  skin  of  the  abdomen. 
Nystrom  reports  that  touching  the  gastric  mucosa  of  a  man  having 
gastric  fistula  with  a  hot  piece  of  metal  or  piece  of  ice,  does  not 


THE  SENSIBILITY  OF  THE  GASTRIC  MUCOSA  105 

call  forth  any  definite  temperature  sensations.  According  to 
Hertz  the  hot  or  cold  sensations  felt  in  the  epigastrium,  upon  swal- 
lowing hot  or  cold  water,  come  from  the  lower  end  of  the  esophagus. 
The  water  accumulates  here  before  the  cardiac  orifice  opens,  and 
that  part  of  the  esophagus  is  thus  stimulated  more  than  the  parts 
above.  He  defends  his  conclusion  by  this  observation:  by  auscul- 
tation over  the  epigastrium  after  swallowing  a  mouthful  of  very 
hot  or  cold  water,  one  will  find  that  immediately  after  the  second 
deglutition  sound,  which  occurs  after  the  last  trace  of  food  has 
entered  the  stomach,  the  hot  or  cold  sensation  disappears.  He 
also  states  that  upon  injecting  hot  or  cold  water  through  a  double 
rubber  tube,  no  temperature  sensation  was  noticed  before  3  or  4 
ounces  had  passed  into  the  stomach.  An  ill-defined  temperature 
sensation  was  then  experienced,  but  he  concludes  that  this  was 
due  to  the  conduction  of  heat  or  cold  to  the  esophageal  wall. 
Hence,  according  to  Hertz,  the  stomach  mucosa  is  not  endowed 
with  heat  or  cold  nerve-endings.  Quincke  introduced  hot  and  cold 
water  into  the  stomach  of  a  boy  with  a  gastric  fistula  and  reports 
that  the  patient  experienced  vague  heat  or  cold  sensations.  Neu- 
mann and  Roux,  injecting  hot  and  cold  water  into  the  stomach 
through  a  double  rubber  tube,  experienced  hot  and  cold  sensations 
in  the  stomach,  the  cold  sensations  being  the  more  pronounced. 
Head,  Rivers,  and  Sherren  injected  water  at  different  temperatures 
into  the  colon  of  a  patient,  upon  whom  a  colostomy  had  been 
performed,  and  found  that  water  at  20°  to  40°  C.  produced  no 
sensation  at  all,  but  water  at  50°  C.  and  very  cold  water  did  give 
rise  to  temperature  sensations,  but  that  these  sensations  were  by 
no  means  as  pronounced  and  as  easily  localized  as  those  produced 
by  applying  water  at  the  same  temperatures  to  the  skin.  Head 
concludes  that  the  viscera  is  endowed  with  ^'protopathic"  tem- 
perature sensibiHty  only. 

Boring  reports  that  water  at  40°  C.  produces  a  sensation  of 
warmth,  and  water  at  30°  C.  a  sensation  of  cold  referred  to  the 
stomach.  In  his  first  paper  Boring  inclined  to  the  view  that  these 
sensations  originate  not  in  the  stomach  but  in  the  abdominal  wall; 
in  the  second  paper  he  concludes  that  they  arise  either  in  the  stomach 


io6        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

itself  or  in  tissues  closer  to  the  stomach  than  the  abdominal  wall 
and  the  esophagus. 

It  is  thus  evident  that  by  far  the  majority  of  those  who  have 
investigated  this  problem  have  experienced  a  vague  hot  or  cold 
sensation,  in  the  region  of  the  epigastrium,  upon  stimulating  the 
stomach  mucosa  with  hot  or  cold  water.  Those  who  do  not  believe 
that  the  sensations  arise  in  the  stomach  mucosa  explain  its  origin 
in  one  of  the  following  ways:  (i)  It  is  due  to  conduction  to  the  skin 
of  the  abdomen.  (2)  It  is  due  to  reflex  vascular  changes  of  the 
skin  of  the  abdomen.  (3)  It  is  projected  from  the  esophagus.  (4) 
It  arises  in  the  lower  part  of  the  esophagus. 

Our  own  experiments  on  Mr.  V.  and  on  ourselves  go  to  show 
that  the  above-mentioned  theories  are  untenable.  That  is  to  say, 
we  find  that  the  gastric  mucosa  is  endowed  with  protopathic  tempera- 
ture sensibility. 

The  first  series  of  experiments  was  on  Mr.  V.  He  was  blind- 
folded and  was  not  told  the  nature  of  the  experiments.  The  water, 
40  to  60  c.c,  was  injected  through  a  small  rubber  tube  which  was 
passed  through  the  large  permanent  tube  of  the  fistula.  With 
water  at  50°  C.  he  said  that  he  felt  a  hot  sensation  in  the  stomach, 
after  a  latent  period  of  about  5  seconds.  When  the  same  amount 
of  water  at  10°  C.  was  injected,  a  cold  sensation  was  felt  after  a 
sHghtly  shorter  latent  period.  A  metal  rod  5  mm.  in  diameter, 
heated  to  about  50°  C,  was  passed  down  through  the  fistula 
catheter  until  the  end  touched  the  mucosa  of  the  dorsal  wall  of 
the  stomach.  A  longer  latent  period  elapsed  here  before  any 
sensation  of  heat  was  noticed.  When,  however,  a  small  piece  of 
ice,  held  by  a  pair  of  forceps,  was  brought  into  contact  with  the 
stomach  mucosa,  the  latent  period  was  not  much  longer  than  when 
cold  water  had  been  injected.  A  cold  sensation  was  distinctly  felt. 
These  experiments  were  repeated  over  and  over  again,  and  Mr.  V. 
was  invariably  able  to  recognize  whether  the  mucosa  was  being 
stimulated  with  hot  or  cold  media,  provided  the  media  was  45  to 
55°  C.  and  the  cold  at  least  13°  C. 

The  temperature  sensations  initiated  by  touching  the  gastric 
mucosa  directly  with  hot  or  cold  soHds  cannot  come  from  the 


THE  SENSIBILITY  OF  THE  GASTRIC  MUCOSA  107 

stimulation  of  the  esophageal  mucosa.  The  latent  period  is  too 
short  to  allow  temperature  conductions  to  the  skin  of  the  abdomen. 
But  since  it  is  possible  that  the  cardia  and  the  lower  end  of  the 
esophagus  of  Mr.  V.  are  patent,  water  injected  through  the  fistula 
may  reach  the  lower  end  of  the  esophagus.  This  possibility  was 
guarded  against  in  a  second  series  of  experiments,  where  we  injected 
the  hot  and  cold  water  into  a  very  delicate  rubber  balloon  previously 
introduced  into  the  stomach.  The  hot  and  cold  water  was  correctly 
recognized  as  hot  or  cold,  just  as  in  the  test  with  the  water  touching 
the  mucosa  directly,  the  only  difference  being  a  somewhat  longer 
latent  period.  It  is  clear  from  the  above  that  the  gastric  mucosa 
of  Mr.  V.  is  endowed  with  protopathic  temperature  sense. 

A  third  series  of  experiments  was  carried  out  on  the  author  and 
on  one  assistant  (Mr.  B.).  Three  rubber  tubes  of  suitable  size  were 
placed  one  inside  the  other  so  as  to  have  three  walls  of  rubber  and 
two  air  spaces  between  the  liquid  in  the  inside  tube  and  the  eso- 
phageal mucosa,  for  the  purpose  of  retarding  heat  conduction.  The 
inside  tube  had  a  diameter  of  3  mm.  The  subject  was  blindfolded 
and  50  c.c.  of  water  at  50°  C.  were  injected  into  the  stomach.  A 
sensation  of  heat  was  noted  about  10  to  15  seconds  after  the  injec- 
tion, and  about  60  seconds  before  enough  conduction  had  taken 
place  to  cause  the  tube  to  feel  warm  in  the  mouth  and  throat. 
When  the  same  amount  of  water  at  10°  C.  was  injected,  a  definite 
cold  sensation  was  felt  from  5  to  10  seconds  after  the  injection  had 
commenced  and  about  60  seconds  before  the  tube  began  to  feel 
cold  to  the  fingers  or  to  the  throat. 

Both  of  us  experienced  hot  and  cold  sensations  and  never  made 
the  mistake  of  confusing  the  heat  sensation  with  the  cold  sensation. 
Confirming  Neumann  and  others,  we  found  the  cold  sensation  to 
be  more  distinct  and  better  localized  than  the  heat  sensation. 

This  certainly  does  not  seem  to  indicate  that  the  stomach 
mucosa  is  devoid  of  temperature  sensations,  nor  that  this  sensa- 
tion is  projected  from  the  esophagus,  as  has  been  suggested  by  a 
number  of  investigators.  However,  there  is  a  possibility  that  some 
of  the  water  might  reach  the  wall  of  the  lower  end  of  the  esophagus 
by  being  forced  up  along  the  tube.    In  view  of  the  small  amount 


io8        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

of  water  necessary  to  evoke  the  hot  and  cold  sensations  and  in 
view  of  the  short  latent  period  mentioned  above,  this  seems  very 
unlikely. 

To  make  sure  that  the  sensation  did  not  arise  as  a  result  of  the 
stimulation  of  the  esophagus,  as  well  as  to  prove  that  the  sensation 
is  not  due  to  conduction  to  the  skin  of  the  abdomen,  or  to  reflex 
vascular  changes  in  the  skin  of  the  abdomen,  a  fourth  series  of 
experiments  was  performed.  For  these  experiments  a  rubber  tube 
I  cm.  in  diameter  was  used.  Inside  this  large  tube  we  placed  two 
smaller  tubes,  side  by  side;  one  of  these  was  5  mm.  in  diameter 
and  the  other  was  3  mm.  The  smaller  of  these  two  tubes  was  not 
pulled  clear  through  the  outside  tube,  but  only  so  far  that  its 
lower  end  was  about  an  inch  above  the  lower  end  of  the  outside 
tube.  The  5  mm.  tube  was  pulled  through  the  outside  tube  so 
that  it  extended  about  10  cm.  below  the  lower  end  of  it.  A  small 
glass  tube  5  mm.  long  was  now  forced  up  into  this  longer  tube  as 
far  as  to  the  lower  end  of  the  outside  tube.  The  lower  end  of  the 
outside  tube  was  then  tied  securely  about  the  longest  tube  at  this 
point.  This  apparatus  was  now  swallowed  far  enough  down,  so 
that  the  lower  end  of  the  outside  tube  reached  just  through  the 
cardiac  orifice.  The  longest  tube,  the  end  of  which  of  course  was 
open,  therefore  extended  far  down  into  the  stomach.  The  smallest, 
whose  lower  end  was  within  an  inch  of  where  the  outside  tube 
was  tied,  that  is,  within  2  to  3  cm.  of  the  cardia,  was  now  con- 
nected with  a  pressure  bottle.  It  had  previously  been  found  that 
hot  water,  in  passing  through  a  glass  tubing  and  connections  of 
the  pressure  bottle,  lost  approximately  8°  C,  and  that  water  placed 
in  the  bottle  at  10°  C.  was  raised  to  12°  C.  in  passing  through. 
Water  at  58°  C.  was  now  placed  in  the  pressure  bottle  and  per- 
mitted to  flow  down  through  the  smallest  inside  tube.  It  naturally 
was  forced  up  again  between  and  around  the  two  inside  tubes. 
By  so  doing  the  heat  was  conducted  through  the  wall  of  the  outside 
tube  and  stimulated  the  heat  nerve-endings  in  the  esophagus,  so 
that  a  definite  heat  sensation  was  felt  along  its  whole  course,  as 
well  as  in  the  mouth  and  pharynx.  The  striking  feature  about 
this,  however,  was  that,  although  the  walls  of  the  lower  end  of  the 


THE  SENSIBILITY  OF  THE  GASTRIC  MUCOSA  109 

outside  tube  naturally  became  hot  before  those  of  the  upper,  the 
heat  sensation  was  first  felt  in  the  mouth  and  throat  and  then 
gradually  traveled  down  the  whole  length  of  the  esophagus.  At 
all  times,  however,  the  heat  sensation  was  more  intense  in  the 
throat  and  in  the  upper  part  of  the  esophagus  than  in  its  lower 
end.  While  the  walls  of  the  esophagus  were  thus  being  stimulated, 
50  c.c.  of  water  at  50°  to  55°  C.  was  injected  into  the  stomach 
through  the  longest  inside  tube  which  opened  into  the  stomach,  and 
after  a  latent  period  of  about  10  seconds,  a  spreading  heat  sensa- 
tion was  felt  lower  down  than  that  resulting  from  the  stimulation 
of  the  esophagus.  The  sensation  also  seemed  better  localized  than 
that  from  the  esophagus,  so  that  it  was  not  very  difficult  to  keep 
the  two  sensations  apart  in  consciousness.  The  reason  for  the 
better  localization  might,  of  course,  be  due  to  the  fact  that  more 
nerve-endings  were  stimulated  in  the  stomach  mucosa,  as  the 
water  came  into  direct  contact  with  it,  than  in  the  case  of  the 
esophagus,  where  probably  the  rubber  tube  did  not  come  into 
contact  with  the  mucosa  at  all  points. 

When  water  at  10°  C.  was  placed  in  the  pressure  bottle — the 
outside  tube  stimulating  the  esophagus  thus  being  filled  by  water 
at  12°  C.  and  50  c.c.  of  water  at  12°  C.  was  injected  into  the  stomach, 
a  distinct,  spreading,  cold  sensation  was  felt  lower  than  that  result- 
ing from  the  stimulation  of  the  esophagus.  There  was  no  difficulty 
in  recognizing  two  separate  and  distinct  cold  sensations,  one  coming 
from  the  esophagus  and  the  other  from  the  stomach. 

While  the  esophagus  was  being  stimulated  by  water  at  12°  C. 
in  this  tube  system,  a  water  bottle  which  was  filled  with  water  at 
12°  C.  was  placed  on  the  skin  of  the  abdomen.  The  two  cold 
sensations  resulting  could  easily  be  kept  apart  in  consciousness. 
Next,  50  c.c.  of  water  at  the  same  temperature  were  injected  into 
the  stomach,  and  a  third,  distinct,  spreading,  cold  sensation  was 
felt  in  the  stomach.  This  experiment  was  repeated  several  times 
with  hot  and  cold  water,  as  indicated  above,  and  with  the  same 
results. 

If  the  temperature  sensation  felt  on  introducing  hot  or  cold 
liquids  into  the  stomach  is  due  to  heat  conduction  through  to  the 


no        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

skin  of  the  abdomen^  or  to  reflex  vascular  changes  in  the  skin  of 
the  abdomen,  or  is  projected  from  the  esophagus,  how  is  it  possible 
that  one  can  distinguish  in  consciousness  the  sensations  coming 
from  the  esophagus,  the  stomach,  and  the  skin,  at  the  same  time, 
when  each  is  being  stimulated  by  water  at  the  same  temperature, 
as  shown  above  ? 

To  make  sure  that  the  sensation  was  not  due  to  conduction 
through  the  abdominal  wall  to  the  skin  of  the  abdomen,  the  bulb 
of  a  thermometer  was  pressed  close  to  the  skin  over  the  stomach 
and  covered  with  absorbent  cotton.  After  it  had  become  stable, 
200  c.c.  of  water  at  10°  C.  were  injected  into  the  stomach  and  the 
mercury  in  the  thermometer  watched  for  a  period  of  5  minutes. 
This  was  repeated  several  times.  In  each  case,  after  a  latent  period 
of  5  "minutes,  the  mercury  had  fallen  only  a  small  fraction  of  a 
degree.  It  is  therefore  evident  that  the  cold  sensation  which  one 
feels  after  a  latent  period  of  from  5  to  10  seconds,  after  the  injection 
of  20  c.c.  of  cold  water  into  the  stomach,  is  not  due  to  conduction 
through  the  abdominal  wall  and  stimulation  of  the  nerve-endings 
in  the  skin. 

Boring  has  shown  that  500  c.c.  of  water  at  0°  C.  in  the  stomach 
lowers  the  skin  temperature  only  0.05°  C.  It  is  therefore  out  of 
the  question  that  25  c.c.  of  water  in  the  stomach  at  25°  to  30°  C. 
stimulate  the  temperature  end  organs  in  the  skin.  Moreover,  the 
adequate  temperature  stimulus  in  the  stomach  cavity  is  less  than 
5°  above  and  10°  below  the  body  temperature. 

We  agree  with  Hertz  that  when  one  swallows  a  mouthful  of 
ice  water,  the  most  intense  cold  sensation  seems  to  come  from  the 
lower  end  of  the  esophagus,  and  that  this  is  undoubtedly  due  to 
the  fact  that  the  water  accumulates  there  and  is  detained  for  a 
shorter  or  longer  period  before  the  cardiac  orifice  opens  so  that  it 
can  flow  into  the  stomach.  He  further  states  that  the  cold  sensa- 
tion disappears  after  the  water  has  entered  the  stomach.  This 
we  cannot  corroborate.  We  invariably  feel  a  vague,  spreading, 
cold  sensation  after  the  water  has  entered  the  stomach,  which 
disappears  after  a  few  seconds.  Even  if  it  were  the  case  that  no 
cold  sensation  could  be  felt  after  the  water  had  passed  into  the 


THE  SENSIBILITY  OF  THE  GASTRIC  MUCOSA  iii 

stomach,  this  could  not  prove  that  the  stomach  mucosa  is  devoid 
of  heat  and  cold  nerve-endings.  In  the  first  place,  a  mouthful  of 
cold  water  in  passing  down  into  the  stomach  is  warmed  sufficiently 
to  raise  its  temperature  several  degrees.  On  this  account  the  nerve- 
endings  in  the  mucosa  of  the  stomach  are  not  stimulated  as  intensely 
as  are  those  in  the  esophagus.  The  empty  stomach  contains  lo  to 
50  c.c.  of  fluid  at  38°  C.  which  rapidly  mixes  with  and  thus  raises 
the  temperature  of  the  swallowed  water.  It  is  also  well  known 
that  stronger  impulses,  reaching  the  central  nervous  system  from 
one  part,  tend  to  suppress  in  consciousness  weaker  impulses  of 
the  same  nature,  reaching  it  from  some  other  part,  so  that  it  is 
difficult  to  separate  the  two  sensations  in  consciousness. 

From  our  experiments  we  conclude:  (i)  The  stomach  mucosa  is 
endowed  with  heat  and  cold  nerve-endings.  (2)  These  fibers  are,  as 
Head  suggests,  of  the  protopathic  type;  that  is,  they  are  not  stimu- 
lated by  sKght  temperature  changes,  or  if  they  are,  the  impulses  do 
not  affect  consciousness.  (3)  They  are  more  abundant,  or  more 
readily  stimulated  in  the  throat  and  esophagus  than  in  the  stomach. 

IV.      THE   SENSATION  OF  FULNESS  AND   SATIETY 

All  who  have  studied  the  origin  of  the  sensations  of  fulness  and 
satiety  seem  to  agree  that  they  do  not  originate  in  the  mucosa  of 
the  stomach,  and  our  own  results  agree  with  this  view.  The 
literature  is  extensively  reviewed  by  Hertz. 

Hertz  and  his  co-workers  inflated  the  stomach  of  two  healthy 
men  with  air  through  a  tube  connected  with  a  manometer.  They 
found  that  a  '' sensation  of  fulness  or  tightness  in  the  upper  part 
of  the  abdomen,  associated  with  a  desire  to  eructate,  was  felt  as 
soon  as  the  intragastric  pressure  reached  respectively  12  and  14  mm. 
of  mercury  in  the  two  cases.  The  pressure  fell  after  20  seconds  by 
approximately  2  mm.,  owing  apparently  to  relaxation  of  the  tone 
of  the  stomach,  and  simultaneously  the  sensation  of  fuhiess  dis- 
appeared. Now,  on  slowly  injecting  more  air,  the  pressure  gradu- 
ally rose  to  its  original  height  and  the  sensation  reappeared;  it 
again  disappeared  after  20  seconds,  the  pressure  simultaneously 
falling  2  mm.,  after  which  it  remained  constant.    Exactly  the  same 


112        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

rise  in  pressure  and  the  same  sensation  of  fulness,  followed  by  a  fall 
of  pressure  and  a  disappearance  of  the  sensation,  were  produced 
four  times  in  succession  by  injecting  air,  none  being  allowed  to 
escape  in  the  interval.  These  observations  proved  that  the  tension 
exerted  from  within  on  the  circular  muscle  fibers  of  the  stomach  is 
the  cause  of  the  sensation  of  fulness." 

That  this  is  the  main  source  of  its  origin  seems  quite  clear. 
There  is  a  possibility  that  the  stretching  of  the  abdominal  muscles 
as  well  as  the  pressure  on  other  structures  in  the  abdominal  cavity 
contribute  to  the  sensation  of  fulness.  As  a  proof  that  this  element 
has  little  if  any  significance  in  giving  rise  to  the  sensation,  Hertz 
related  experiments  on  persons  with  atonic  stomachs.  When  6  gm. 
each  of  sodium  bicarbonate  and  tartaric  acid  are  swallowed  sepa- 
rately, 1,700  c.c.  of  carbon  dioxide  are  given  off  under  atmos- 
pheric pressure  at  body  temperature.  This  invariably  causes  an 
unpleasant  and  sometimes  painful  sensation  of  fulness  in  normal 
individuals,  while  in  persons  with  atonic  stomachs  it  does  not 
cause  any  sensation  of  fulness.  Hertz,  therefore,  concludes  that 
''the  sensation  of  fulness  in  the  stomach  is  due  to  tension  on  its 
muscular  coat,  and  depends  very  little  and  only  in  extreme  cases 
on  the  stretching  of  the  abdominal  wall." 

To  these  observations  of  Hertz  we  can  add  our  negative  findings 
in  regard  to  the  gastric  mucosa  as  a  contributing  factor.  Chemical 
or  mechanical  stimulation  of  the  mucosa  (whether  the  stomach  is 
in  strong  or  in  feeble  tonus)  never  produces  a  sensation  similar 
to  that  of  fulness.  At  the  same  time,  it  must  be  noted  that  mere 
tension  on  the  muscular  coats,  that  is,  intragastric  pressure,  will  not 
under  all  conditions  give  rise  to  the  sensation.  The  degree  of  intra- 
gastric pressure  required  to  cause  a  feeling  of  fulness,  according 
to  Hertz,  is  frequently  exceeded  at  the  height  of  a  period  of  hunger 
contractions  of  the  empty  stomach,  when  a  distended  balloon  is 
in  the  stomach,  yet  the  sensation  referred  to  the  epigastrium  in 
these  conditions  is  that  of  emptiness,  not  fulness.  It  is  therefore 
clear  that  a  certain  amount  of  tonus  reaction  of  the  stomach  must 
be  present  before  tension  or  pressure  on  the  walls  of  the  stomach 
produce  the  sensation  of  fulness. 


THE  SENSIBILITY  OF  THE  GASTRIC  MUCOSA  113 

The  sensation  of  satiety  felt  after  an  abundant  and  palatable 
meal  involves  several  factors,  none  of  which  appear  to  depend 
primarily  on  the  nerves  in  the  gastric  mucosa.  One  must  have 
some  degree  of  hunger  and  appetite  before  eating,  the  food  must 
be  palatable,  and  enough  food  must  be  consumed  to  produce 
moderate  distension  of  the  stomach.  If  either  of  these  factors  is 
lacking,  complete  satiety  is  not  felt  after  the  meal.  One  may  feel 
great  hunger  and  consume  unpalatable  food  till  the  sensation  of 
fulness  develops,  but  satiety  does  not  follow.  If  the  hunger  factor 
is  present  and  the  food  is  to  the  king's  taste,  but  of  insufficient 
bulk,  although  more  than  ample  for  the  needs  of  nutrition,  satiety 
is  also  lacking.  Hence  the  sensation  complex  of  satiety  involves 
the  element  of  contrast  between  the  uncomfortable  tension  of 
hunger  and  the  sensation  of  fulness,  together  with  the  lingering 
memories  of  the  taste  and  smell  of  the  food.  Normal  motor,  secre- 
tory, and  sensory  functions  in  the  stomach  are  thus  a  prerequisite 
rather  than  a  direct  factor  in  the  genesis  of  satiety. 

V.      NAUSEA   OF   GASTRIC   ORIGIN 

The  sensation  complex  of  nausea  and  vomiting  can  be  initiated 
by  stimulation  of  nerves  in  the  gastric  mucosa;  but  many  of  the 
sensory  elements  in  nausea  involve  mechanism  outside  the  stomach. 
When  nausea  is  induced  by  the  odor,  sight,  or  taste  of  disgusting 
substances,  or  by  the  memory  of  such  substances  we  may  call  it 
strictly  physiological  processes.  But  most  cases  of  nausea  are 
due  to  pathological  processes  or  disease.  Some  of  these  patho- 
logical conditions  are  pressure,  partial  anemia,  or  action  of  specific 
toxic  substance  on  the  medulla ;  intense  and  prolonged  pains  of  peri- 
pheral origin,  toxemias,  hyper  excitability,  or  excessive  stimulation 
of  the  visceral  nerves. 

The  sensation  of  nausea  is  very  complex.  A  certain  feel- 
ing of  bodily  weakness  and  a  characteristic  pain  and  distress 
(''sinking  feeling")  in  the  stomach  are  always  present.  With 
these  one  may  also  experience  headache,  dizziness,  chills  (from 
cutaneous  vasoconstriction  and  perspiration),  formication,  etc. 
The  violent  contractions  of  the  pyloric  end  of  the  stomach  pre- 


114        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

ceding  and  accompanying  the  act  of  vomiting  may  even  be  felt 
as  painfuL 

When  nausea  is  produced  by  excessive  or  destructive  stimulation 
of  the  normal  gastric  mucosa,  or  by  what  may  be  called  normal 
stimulation  (water,  food,  gastric  juice,  etc.)  of  a  hyperexcitable 
mucosa,  what  sensory  elements  in  nausea  are  due  to  this  stimula- 
tion directly?  Since  strong  contractions  of  the  stomach  cause  a 
pressure-pain  sensation,  and  excessive  stimulation  of  the  mucosa 
may  also  cause  pain,  it  is  evident  that  the  tension,  pressure,  and 
pain  referred  to  the  epigastric  region  in  nausea  are  of  peripheral 
or  gastric  origin.  The  peculiar  ''sinking  feeling"  or  the  feeling 
of  "helplessness"  is  probably  in  the  main  also  a  direct  effect  of 
the  gastric  states.  At  any  rate  that  feeling  is  not  experienced 
except  in  nausea  sufficiently  intense  to  approach  vomiting.  The 
weakness,  dizziness,  and  headache  are  probably  in  the  main  indi- 
rect effects,  that  is,  due  to  disturbances  in  the  circulation. 

Michael  Foster  considered  ''nausea  allied  to  hunger."  Boring 
states  that  some  of  his  subjects  (normal  men)  confused  mild  nausea 
with  the  sensation  of  hunger.  Thus  5  per  cent  of  hydrochloric 
acid  put  directly  into  the  stomach  by  a  tube  produced  gastric  pain 
identical  with  hunger,  except  that  it  was  more  continuous.  One 
of  Boring's  men  who  was  subject  to  spells  of  indigestion  reports 
"when  I  feel  nauseated  [from  indigestion]  I  generally  stop  eating. 
I  begin  with  my  meals  again  as  soon  as  I  feel  hungry,  but  I  cannot 
always  tell  whether  I  am  hungry  or  still  nauseated." 

We  believe  this  fusion  or  confusion  of  nausea  with  hunger  is 
either  pathological  or  else  due  to  superficial  analysis.  It  is  true 
that  the  gastric  factors  in  both  hunger  and  nausea  are  uncomfort- 
able tension  and  pain;  that  hunger  as  well  as  nausea  causes  saH- 
vation ;  that  in  some  people  hunger  as  well  as  nausea  includes  bodily 
weakness,  headache,  etc.,  but  the  distinct  "sickness"  character  of 
the  gastric  distress  in  nausea  is  not  even  present  in  any  stage  of 
hunger  in  normal  persons.  Hunger  involves  the  kinesthetic  nerves 
of  the  stomach,  while  nausea  is  caused  by  stimulation  of  nerves  in 
the  gastric  mucosa.  The  central  effects  of  hunger  and  nausea 
in  normal  persons  are  also  different.    Hunger  is  compatible  with 


THE  SENSIBILITY  OF  THE  GASTRIC  MUCOSA         -  115 

and  intensifies  appetite  and  desire  for  food,  while  nausea  and  appe- 
tite are  mutually  exclusive.  But  since  hunger  is,  and  nausea  may 
be,  caused  by  stimulation  of  gastric  nerves,  it  is  likely  that  in 
persons  with  hypersensitive  vagi,  or  with  unstable  central  nervous 
organization,  strong  hunger  may  contain  elements  of  nausea,  or 
actually  pass  into  nausea. 

Normal  persons  may  experience  hunger  pangs  and  something 
like  mild  nausea  or  ^'sick  stomach"  at  the  same  time,  without 
confusing  the  two  sensations,  provided  there  is  a  certain  degree 
of  hyperexcitability  of  the  nerves  in  the  gastric  mucosa.  This 
was  noted  by  the  author  on  the  fifth  day  of  starvation.  On  that 
day  the  sensation  of  hunger  was  tinged  with  a  ^'burning"  sensation 
also  referred  to  the  stomach.  This  sensation  was  probably  caused 
by  pressure  or  acid  stimulation  of  hyperexcitable  nerve-endings 
in  the  gastric  mucosa.  It  is  known  that  prolonged  starvation 
leads  to  such  hyperexcitability,  and  in  this  case  there  was  addi- 
tional indications  of  it  in  the  nausea  caused  by  smoking. 

VI.      THE   GASTRIC  ELEMENT   OF  APPETITE 

Substances  like  strong  alcohol  or  acid  (5  to  20  per  cent  HCl), 
mustard,  pepper,  etc.,  introduced  by  tube  directly  into  the  stomach 
in  sufficient  quantities,  cause  varying  degrees  of  pain,  accompanied 
at  first  with  a  peculiar  feeling  of  warmth  in  the  stomach.  In 
concentrations  sufficient  to  cause  pain,  all  chemicals  evidently 
injure  the  mucosa  and  its  nerve-endings,  as  shown  by  the  develop- 
ment of  gastritis.  Boring  states  that  the  pain  induced  by  2  to  10 
per  cent  HCl  in  the  stomach  is  identical  with  the  pangs  of  hunger, 
and  surmises  that  the  acid  in  the  stomach  causes  gastric  hunger 
contractions.  This  surmise  is  contrary  to  all  experimental  facts,  at 
least  on  normal  men  and  dogs. 

When  these  and  other  chemical  substances  are  put  into  the 
stomach  too  dilute  to  cause  ache,  pain,  or  discomfort,  their  contact 
with  the  normal  gastric  mucosa  still  aifects  consciousness,  but  in 
a  manner  the  very  opposite  to  that  of  pain.  The  sensation  pro- 
duced by  this  gentle  chemical  stimulation  of  the  mucosa  has  a 
character  of  its  own  that  resembles  if  it  is  not  identical  with  appe- 


Ii6        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

tite.  We  cannot  understand  how  Hertz  and  Schmidt  could  have 
reached  the  conclusion,  on  the  basis  of  experiments  on  man,  that 
the  normal  mucosa  is  insensitive  to  chemical  stimuli,  including  2 
per  cent  mineral  acids  (HCl) . 

Pavlov  concludes  that  ^'the  tactile  sensation  of  the  stomach 
at  the  moment  of  entry  of  food  is  capable  of  awakening  or  increasing 
appetite."  In  the  experiments  cited  by  Pavlov  in  support  of  this 
conclusion  the  stimulation  of  the  nerve-endings  in  the  mouth  and 
in  the  esophagus  was  not  excluded. 

The  author,  working  on  himself,  soon  recognized  that  moderate 
chemical  stimulation  of  the  nerve-endings  in  the  gastric  mucosa 
modified  the  flow  of  consciousness,  although  this  modification  did 
not  consist  in  the  sensation  of  hunger.  This  can  readily  be  experi- 
enced by  anyone  who  is  sufficiently  interested  to  try,  by  introducing 
moderately  cold  water,  beer,  wine,  weak  acids  (0.5  to  2.0  per  cent 
HCl),  weak  alcohol,  or  carbonated  drinks  through  a  tube  into  the 
stomach  so  as  to  avoid  stimulation  of  nerve-endings  in  the  mouth 
and  esophagus.  The  sensation  produced  by  these  substances  in 
the  stomach  is  rather  transitory,  but  may  persist  for  several  min- 
utes. With  the  exception  of  cold  water,  which  is  also  felt  as  cold, 
these  various  substances  give  rise  to  a  characteristic  sensation 
which  fuses  with,  or  cannot  be  distinguished  from  appetite.  It 
is  like  the  sensation  of  increased  appetite  experienced  by  most 
people  at  the  beginning  of  a  meal,  after  eating  a  few  morsels  of 
palatable  food.  The  sensation  is  pleasant,  and  turns  the  attention 
toward  food  and  eating. 

We  are  accustomed  to  think  that  the  substances  named  above 
affect  consciousness  solely  through  stimulation  of  nerve-endings 
in  the  mouth.  This  view  is  no  longer  tenable.  By  introducing 
these  substances  through  the  stomach  tube  at  the  height  of  a 
gastric  hunger  contraction,  one  actually  experiences  a  successive 
contrast  of  the  sensations  of  hunger  and  appetite,  as  these  substances 
temporarily  inhibit  the  hunger  contractions  in  stimulating  the  gas- 
tric mucosa.  From  the  first  it  was  clear  that,  when  beer  or  cold  or 
hot  water  was  first  introduced  into  the  stomach  during  a  vigorous 
hunger  contraction,  the  sensation  resulting  was  the  exact  opposite 


THE  SENSIBILITY  OF  THE  GASTRIC  MUCOSA  117 

of  that  caused  by  the  hunger  contraction.  In  place  of  an  unpleasant 
tense  sensation,  associated  with  restlessness,  the  sensation  caused 
by  these  different  stimuli  is  one  of  relief.  A  pleasant,  tingling  sensa- 
tion is  felt  in  the  stomach.  One  feels  perfectly  at  ease,  but  the 
thoughts  tend  to  revert  to  the  dinner  table.  At  first,  we  were  not 
able  to  say  just  what  this  sensation  was  like,  although  it  was  a 
famihar  one.  After  paying  close  attention  to  the  sensation  experi- 
enced at  meals  just  after  a  few  mouthfuls  of  good  food  or  drink 
have  been  swallowed,  we  became  convinced  that  the  two  sensations 
are  very  much  alike,  if  not  identical. 

How  do  we  know  that  the  sensation  temporarily  produced  by 
the  above-named  substances  in  the  stomach  is  directly  due  to 
stimulation  of  nerve-endings  in  the  gastric  mucosa?  Since  the 
introduction  of  these  substances  in  the  stomach  inhibits  the  gastric 
tonus  and  the  gastric  hunger  contractions,  may  not  the  sensation 
be  one  of  negative  character,  so  to  speak,  that  is,  diminution  or 
absence  of  hunger?  We  are  in  position  to  answer  this  question 
definitely  in  the  negative.  In  the  first  place,  the  sudden  and 
spontaneous  relaxation  of  the  stomach  at  the  end  of  a  period  of 
gastric  hunger  contractions  is  accompanied  by  a  characteristic 
sense  of  relief  and  disappearance  of  a  certain  tension  or  unpleasant 
mental  stress,  but  this  sensation  complex  has  not  the  positive 
character  that  directs  attention  to  food  and  eating.  It  is  essentially 
relief  from  pain.  Secondly,  putting  these  substances  into  a  stomach 
which  is  quiescent  and  very  greatly  relaxed,  nevertheless,  inaugu- 
rates this  temporary  appetite  or  appetite-like  sensation.  Hence 
we  conclude  that  it  is  directly  induced  by  stimulation  of  certain 
nerve-endings  in  the  gastric  mucosa  itself.  Of  course,  if  the  nerve- 
endings  in  the  gastric  mucosa  are  thus  stimulated  at  the  time  the 
muscularis  is  in  strong  tonus  and  hunger  contractions,  the  appetite- 
like sensation  is  fused  with  that  of  relief  from  the  pangs  of  hunger. 

It  is  significant  that  normal  human  gastric  juice  having  full 
acid  strength  (0.45  to  0.50  per  cent  free  HCl)  is  capable  of  inducing 
this  sensation  from  the  stomach.  This  has  been  verified  repeatedly 
by  introducing  50  c.c.  of  appetite  gastric  juice  into  Mr.  V.  through 
the  stomach  tube.    Gastric  juice  of  weaker  acidity  (0.20  per  cent) 


Ii8        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

does  not  have  this  effect.  As  this  full-strength  gastric  juice  is 
rapidly  secreted  in  the  stomach  at  the  beginning  of  eating,  it  is 
probably  a  factor  in  the  augmentation  of  appetite  by  the  very  act 
of  eating.  It  may  be  pointed  out  that  the  foregoing  facts  permit 
us  to  see  a  suggestion  of  truth  in  Beaumont's  theory  that  turges- 
cence  of  the  gastric  glands  is  the  cause  of  hunger.  In  the  first 
place,  Beaumont,  in  common  with  most  physiologists,  did  not 
clearly  distinguish  between  hunger  and  appetite,  but  used  the  two 
terms  interchangeably.  If  we,  then,  substitute  appetite  for  hunger, 
we  see  that  with  the  stomach  normal,  the  appetite  sensation  may 
be  actually  initiated  or  augmented  by  gastric  juice,  not  through 
mechanical  pressure  of  the  juice  in  the  ducts,  but  by  acid  stimu- 
lation of  nerve-endings  in  the  gastric  mucosa. 

It  need  scarcely  be  pointed  out  that  when  foods  or  liquids  are 
taken  into  the  mouth  and  swallowed  in  the.  normal  way  their 
main  influence  on  appetite  is  by  way  of  nerve-endings  in  the 
mouth.  In  fact,  this  influence  is  so  predominant  that  only  by 
excluding  it  are  we  able  clearly  to  distinguish  the  gastric  factor. 
The  memory  factor  in  appetite  is  therefore  pre-eminently  gustatory 
and  olfactory. 


CHAPTER  VIII 

HUNGER  AND  AGE 

I.      HUNGER  IN  INFANTS 

That  the  young  and  growing  individual  experiences  greater 
hunger  than  the  adult  or  aged  individual  is  common  knowledge. 
This  is  an  obvious  biological  correlation.  In  addition  to  the  forma- 
tion of  new  tissues,  the  young  mammal  is  usually  more  active  than 
the  adult,  and  its  body  surface  is  larger  in  proportion  to  body 
weight,  and  hence  (if  warm-blooded)  he  loses  proportionately  more 
heat.  All  these  factors  call  for  greater  amounts  of  food.  There 
are  a  number  of  conditions  that  may  operate  to  produce  this  greater 
hunger  in  the  young,  (i)  There  may  be  a  greater  rate  of  secretion 
of  gastric  juice,  so  that  the  digestion  in  the  stomach  requires  less 
time.  This  would  give  a  more  continuously  empty  stomach.  (2) 
There  may  be  relative  hypermotiHty  of  the  filled  as  well  as  of  the 
empty  stomach  because  of  the  actual  youth  of  the  stomach  tissues, 
because  of  greater  motor  innervation  from  the  brain  (vagus  tonus), 
or  as  the  result  of  greater  concentration  of  specific  chemical  stimuli 
in  the  blood  correlated  with  the  higher  rate  of  metabolism.  (3) 
There  may  be  greater  sensitiveness  to  afferent  impulses  on  the 
part  of  the  brain  concerned  in  the  hunger  sensation.  Either  factor 
alone,  or  all  combined,  would  result  in  greater  frequency  and 
intensity  of  hunger  and  appetite. 

The  first  question  to.be  determined  is  whether  the  stomach  of 
the  young  exhibits  greater  hunger  contraction  than  the  stomach 
of  adult  and  aged  individuals  of  the  same  species.  On  the  basis 
of  work  done  on  man  and  dogs  this  question  can  now  be  answered 
in  the  affirmative,  at  least  for  these  two  species. 

The  empty  stomach  of  the  newborn  infant  shows  the  periods 
of  gastric  hunger  contractions  before  the  infant  has  had  any  experi- 
ence with  food;  The  hunger  periods  are  more  frequent  in  the 
infant  than  in  the  adult;    that  is  to  say,  the  duration  of  motor 

119 


I20        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

quiescence  of  the  empty  stomach  between  the  hunger  periods  is 
shorter.  In  the  newborn  and  very  young  infant  the  quiescence  of 
the  empty  stomach  lasts  from  lo  to  60  minutes;  in  the  adult 
usually  from  i  to  3  hours. 

This  greater  frequency  of  hunger  in  the  child  is  also  shown  by 
the  more  rapid  development  of  the  hunger  period  after  a  previous 
meal.  In  an  adult  (after  a  full  meal)  gastric  hunger  contractions 
do  not  develop  for  from  4  to  6  hours.  If  the  individual  is  lying  in 
bed,  the  time  is  even  longer.  In  the  normal  breast-fed  infant  the 
average  time  of  appearance  of  a  hunger  period  after  a  full  meal  is 
only  2I  hours. 

Pediatricians  differ  as  to  the  incidence  of  hunger  in  infants, 
because  up  to  the  last  few  years  there  has  been  no  certain  objective 
criterion  for  the  existence  of  hunger.  This  has  led  to  varying  views 
and  practices  in  regard  to  the  frequency  with  which  infants  should 
be  nursed,  some  favoring  an  interval  of  2  hours,  some  one  of  2J  to 
3  hours,  and  some  a  4-hour  interval  between  nursing.  Since  the 
contractions  peculiar  to  the  cardiac  and  fundal  ends  of  the  empty 
stomach  are,  in  normal  individuals  at  least,  an  objective  index  of 
hunger,  the  balloon  method  enables  us  to  determine  the  time  of 
onset  of  hunger  in  infants  after  previous  feeding,  and  the  answer 
to  this  question  may  aid  in  fixing  the  time  that  should  elapse  between 
the  nursings  of  normal  infants. 

Our  observations  were  made  on  thirty  normal  breast-fed  infants, 
from  24  hours  to  4  weeks  old.  In  every  case  the  infant  nursed 
until  it  was  satisfied.  Introduction  of  the  balloon  into  the  stomach 
directly  after  nursing  leads  to  vomiting  of  the  balloon  and  some  of 
the  food.  The  balloon  is  readily  retained  from  45  minutes  to  i 
hour  after  feeding.  Forty-five  observations  were  made  on  the 
thirty  infants.  The  average  time  between  nursing  and  the  appear- 
ance of  the  period  of  hunger  contractions  was  2  hours  and  40 
minutes,  with  a  maximum  of  3  hours  and  30  minutes,  and  a  mini- 
mum of  2  hours  and  20  minutes. 

Our  tracings  show  that  when  the  stomach  is  full  of  food  the 
inflated  balloon  in  the  fundus  reveals  practically  no  contractions. 
As  the  stomach  gradually  empties,  feeble  tonus  contractions  appear, 


HUNGER  AND  AGE  I2i 

and  increase  in  rate  and  intensity  until  they  end  in  a  period  of 
typical  hunger  contractions  from  2J  to  3  hours  after  the  previous 
nursing.  This  change  of  the  tonus  contractions  of  the  fundic  end 
of  the  stomach  partly  filled  with  food  into  the  hunger  contractions 
of  the  empty  stomach  has  already  been  described.  Our  results 
with  the  balloon  method  confirm  the  X-ray  observations  of  Pisek 
and  Le  Wald,  Czerny,  Leo,  and  others,  who  contended  that  the 
emptying  time  of  a  child's  stomach  is  i J  to  3  hours.  The  time 
required  for  emptying  the  stomach  depends,  of  course,  on  the 
quantity  and  quality  of  the  food  as  well  as  on  the  rate  of  the 
gastric  secretion  and  the  vigor  of  the  gastric  digestion  peristalsis. 

In  this  connection  it  may  be  of  interest  to  note  that  the  mam- 
malian infant,  except  when  under  the  strict  control  of  a  pediatrician 
feeds,  on  the  whole,  as  soon  as  the  hunger  sensation  is  strong 
enough  to  be  uncomfortable,  provided  food  is  at  hand;  and  he 
thrives  on  this  procedure;  while  the  infant  whose  routiae  is  ordered 
by  the  pediatrician  nurses  every,  2,  3,  or  4  hours,  irrespective  of 
the  onset  or  intensity  of  the  periods  of  hunger.  Of  course,  a  certain 
period  of  rest  for  the  gastric  glands  may  be  beneficial. 

The  infant's  stomach  shows  feeble  tonus  contractions  of  the 
fundal  end  i  hour  after  nursing.  As  the  stomach  discharges  its 
contents  these  tonus  undulations  gradually  increase  in  frequency 
and  intensity  until  by  the  end  of  from  2^  to  3  hours  these  become 
transformed  into  vigorous  hunger  contractions.  The  time  of  onset 
of  hunger  contractions  after  previous  feeding  varies  for  each  infant. 
In  our  present  series  the  minimimi  is  2  hours  and  the  maximum  3 
hours.  In  the  normal  individual  the  presence  of  vigorous  hunger 
contractions  is  probably  a  biologic  evidence  that  the  stomach  is 
in  proper  condition  to  receive  food.  If  this  is  the  case,  the  stomach 
of  a  normal  infant  is  ready  to  receive  food  from  2  to  3  hours  after 
the  previous  nursing. 

II.      HUNGER  IN  YOUNG  DOGS 

The  experiments  on  dogs  were  made  on  pups  delivered  by 
Caesarian  section  8  to  14  days  before  term,  on  pups  5  weeks  to  5 
months  of  age,  on  young  adults,  and  on  old  adults.    In  all  cases 


122        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

care  was  taken  to  choose  only  dogs  in  good  condition  and  perfect 
health,  as  far  as  could  be  judged  by  actions  and  external  appear- 
ances. Except  in  the  case  of  the  prematurely  born  pups,  the 
observations  were  made  24  hours  after  feeding,  in  order  to  assure  a 
completely  empty  stomach.  The  animals  were  given  at  least  one 
day  or  more  of  rest  after  each  experiment,  so  as  to  be  in  a  perfectly 
normal  condition  when  used  again.  During  the  taking  of  the 
records  they  were  held  in  the  lap,  apparently  without  any  appre- 
ciable discomfort,  for  they  nearly  always  slept  through  a  large  part 
of  the  experiment.  Ten  different  series  of  records  of  the  hunger 
movements  of  the  empty  stomach  were  obtained  from  each  dog 
on  ten  separate  days,  the  continuous  experimental  periods  ranging 
from  2^  to  4J  hours,  respectively. 

The  results  surrtmarized  in  the  accompanying  table  were  com- 
puted from  the  tracings,  and  the  figures  in  each  case  represent 
as  nearly  as  possible  the  true  time  of  activity  and  rest  of  the 
empty  stomach,  everything  in  the  records  of  a  doubtful  charac- 
ter, or  of  an  abnormal  nature  caused  by  disturbing  influences, 
being  eliminated. 

GASTRIC  HUNGER  CONTRACTIONS  IN  DOGS  OF  DIFFERENT  AGES 


Dogs 

Old  adult 

Adult 

Young  adult 

Pup  (age  5  to  6  months) .... 
Young  pup  (age  5  to  6  weeks) 
Prematurely  born  pups.  .  .  . 


Length  of 
Contraction  Period 


Length  of 
Quiescent  Period 


30  min,  to  2  hours 
if  to  3  hours 
2f  to  3!  hours 
3    to  4  hours 
4I  to  sf  hours 
Continuous 


1 6  to  3§  hours 
i|^  to  2  hours 
I  to  i^  hours 
5  to  10  min. 
2.5  to  3.4  min. 
None 


As  regards  variation  of  stomach  movements  between  dogs  of 
different  ages,  the  chief  and  practically  the  only  constant  difference 
was  found  in  the  length  of  the  periods  of  contraction  and  the 
periods  of  quiescence.  In  all  cases  the  periods  of  quiescence  are 
the  longest  in  old  dogs,  varying  from  i^  to  4I  hours,  and  rapidly 
decreasing  in  length  proportionately  to  age  to  2^  to  3  i\  minutes  in 
pups  a  few  days  to  five  or  six  weeks  old.    Conversely  the  periods  of 


HUNGER  AND  AGE  123 

contraction  are  the  longest  in  the  young  dogs — for  instance,  in 
the  very  young  pup  the  recorded  periods  run  from  4J  to  5J 
hours — and  they  rapidly  decrease  in  length  proportionately  to 
age — in  the  old  dogs  from  30  minutes  to  2  hours — thus  showing 
that  the  stomach's  activity  is  in  direct  proportion  to  the  age  of 
the  animal  (Patterson). 

The  rapidity  of  the  strong  hunger  contractions  during  the 
active  periods  appears  on  the  whole  to  be  greater  in  young  animals 
than  in  old.  The  tonus  of  the  stomach  and  also  the  strength  of 
the  contractions  in  young  animals  may  be  slightly  higher,  but  they 
are  subject  to  great  variations.  The  decrease  in  the  activity  of 
the  stomach  as  the  animal  approaches  senility  is  probably  an 
explanation,  in  part  at  least,  of  the  more  chronic  gastric  disturb- 
ances in  the  aged. 

To  summarize:  in  healthy  dogs  the  hunger  contractions  of  the 
empty  stomach  decrease  with  age.  This  decrease  appears  to  some 
extent  in  the  tonus  and  in  the  rapidity  of  the  hunger  contractions, 
but  is  particularly  marked  in  the  duration  of  the  periods  of  hunger 
activity  and  the  intervening  periods  of  quiescence  of  the  stomach. 
On  the  whole,  the  decrease  in  the  gastric  hunger  activity  is  pro- 
portional to  the  advance  in  age.  In  very  young  dogs  the  hunger 
contractions  of  the  empty  stomach  are  practically  continuous. 

Two  factors  are  probably  involved  in  this  age  variation  in  the 
gastric  hunger  contractions,  namely,  (i)  the  actual  age  (reduced 
metabolism)  of  the  motor  tissue  in  the  stomach  itself,  and  (2)  a 
lowering  of  metabolism  in  the  entire  body,  which  may  imply  a 
smaller  quantity  of  chemical  stimuli  to  the  gastric  hunger  mech- 
anism in  the  circulation.  Patterson  attempted  to  determine  the 
relative  importance  of  these  two  factors  by  studying  the  influence  of 
prolonged  starvation  on  the  gastric  hunger  contractions  in  very 
young  and  in  very  old  dogs.  If  the  rate  of  general  body  metabolism, 
that  is,  starvation  metabolism,  is  the  main  factor,  we  should  expect 
that  in  prolonged  starvation  the  gastric  hunger  contractions  of  old 
dogs  would  approach  the  vigor  of  the  normal  hunger  contractions 
of  young  dogs.  This  is  not  the  case.  It  is  true  that  starvation 
causes  some  increase  in  the  vigor  of  the  stomach  tonus  and  con- 


124        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

tractions  in  the  old  dogs.  Starvation  metabolism  of  the  body  in 
general  is  therefore  a  factor.  But  the  actual  age  of  the  stomach 
tissues  is  the  most  important  element.  How  actual  age  of  the 
gastric  motor  mechanism  reduces  the  vigor  and  duration  of  the 
hunger  contractions  cannot  be  answered  until  we  know  what 
constitutes  the  physiological  aging  of  the  tissues. 


CHAPTER  IX 

HUNGER  IN  PROLONGED  STARVATION 

I.      EXPERIMENTS   ON  MEN 

In  the  popular  mind  prolonged  starvation  is  associated  with 
great  pain  and  distress,  despite  reliable  reports  to  the  contrary 
from  many  persons  who  have  undertaken  voluntary  starvation. 
Such  persons  state,  almost  without  exception,  that  after  the  first 
three  or  four  days  of  starvation,  the  sensation  of  hunger  is  no  longer 
felt,  or  at  least  is  not  excessively  painful  or  uncomfortable. 

This  brings  up  some  important  physiological  and  biological 
questions.  If  hunger  ceases  entirely,  or  at  least  loses  its  painful 
urge  after  a  few  days  of  starvation,  what  makes  the  starving 
animal  fight  for  food  as  long  as  his  strength  enables  him  to  move  ? 
In  man  this  struggle  for  food  may  be  due  to  the  desire  to  live  or 
the  fear  of  death,  but  can  we  assume  this  degree  of  conscious  fore- 
sight in  the  lower  animals?  Is  the  reported  absence  of  hunger 
sensation  in  man  after  the  first  few  days  of  starvation  due  to 
failure  of  the  gastric  hunger  mechanism,  or  to  changes  in  the  brain 
that  prevent  the  hunger  impulses  from  reaching  consciousness? 
One  might  naturally  expect  a  decrease  in  the  intensity  of  the  hun- 
ger sensation  when  starvation  reaches  a  point  where  the  brain  and 
stomach  are  greatly  enfeebled  by  loss  of  living  substance  or  by 
too  high  an  acidity  of  the  blood,  but  this  state  is  not  reached  in  a 
healthy  man  by  three  or  four  days'  deprivation  of  food.  If  the 
hunger  mechanism  is  controlled  even  in  part  by  the  starvation 
changes  in  the  tissues  (stomach,  brain)  and  in  the  blood,  we  should 
expect  the  hunger  sensation  to  increase  in  strength  up  to  the  point 
of  tissue  marked  depletion,  unless  the  starvation  itself  sets  up  other 
inhibitory  processes. 

These  questions  can  be  answered  only  by  direct  experiments, 
and  these  were  accordingly  undertaken  both  on  man  and  on  the 
lower  animals.  The  work  on  man  was  carried  out  on  the  author 
and  one  assistant  (Mr.  L.),  in  such  a  way  that  the  gastric  hunger 

"5 


126        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

contractions  and  the  subjective  hunger  sensation  were  recorded, 
day  and  night,  during  the  entire  starvation  period.  In  animals 
below  man  we  can,  of  course,  record  the  gastric  hunger  contractions 
only,  as  we  have  as  yet  no  means  of  determining  the  intensity  or 
quality  of  the  sensations  caused  by  these  contractions. 

During  the  five  days'  starvation  period  the  two  men  continued 
their  usual  work  during  the  day,  and  records  of  the  stomach  tonus 
and  hunger  contractions  were  taken  at  varying  intervals.  During 
the  night  continuous  records  were  taken  beginning  8:00  to  9:00 
P.M.  and  ending  at  5 :  00  to  6 :  00  a.m.  Neither  the  writer  nor  Mr.  L. 
found  much  difficulty  in  sleeping  for  6  to  8  hours  every  night  with 
balloon  and  tube  in  the  stomach.  The  room  was  kept  dark,  except 
for  a  feeble  light  focused  on  the  drum,  so  as  to  enable  the  assistant 
to  take  care  of  the  recording.  And  the  assistant  took  special  care 
to  keep  everything  as  quiet  as  possible.  One  assistant  took  care 
of  the  recording  from  8:00  a.m.  to  2:00  p.m.,  and  a  second  assistant 
from  2:00  P.M.  to  6:00  A.M.  The  time  from  6:00  to  8:00  a.m.  and 
from  6 :  00  to  8 :  00  P.M.  was  usually  spent  in  walking  in  the  parks — ■ 
in  any  event,  outside  the  laboratory. 

I.      THE   OBJECTIVE  PHENOMENA.      THE  HUNGER  CONTRACTIONS 

Before  beginning  the  starvation  period,  observations  on  the 
gastric  hunger  contractions  of  the  writer  were  made  every  second 
or  third  day  for  three  weeks.  These  observations  were  usually 
made  in  the  morning  after  dispensing  with  breakfast,  or  else  during 
the  middle  of  the  day,  thus  dispensing  with  lunch.  No  observa- 
tions were  made  during  night  or  sleep.  These  records  are  quite 
uniform  in  character,  and  represent  the  degree  of  hunger  contrac- 
tions exhibited  by  the  writer's  stomach  6  to  15  hours  after  a  meal. 
We  now  wish  to  direct  the  reader's  attention  to  the  following 
summary  of  the  observations  during  the  starvation  period,  from 
June  29  to  July  4,  19 14. 

A.J.C. 
June  29.    No  breakfast.    First  hunger  period  began  gradually  at  8:45  a.m., 

lasting  for  about  45  minutes;    16  strong  contractions  in  30  minutes. 

A  second  period  ended  at  11:30,  lasting  about  30  minutes.     There 

were  22  strong  contractions  in  30  minutes. 


HUNGER  IN  PROLONGED  STARVATION  127 

Last  meal.    Two  slices  of  toast  and  a  glass  of  milk  at  1 2 :  30  p.m.    Body  weight 

74  kg.;    no  observations  during  the  night. 
June  30.  A.M.     II : 50  to  12 :  20,  fairly  strong  contractions. 
1 2 :  20  to    1 :  50,  quiescence. 
P.M.       1 :  50  to    2 :  30,  18  fairly  Strong  contractions. 
2 :  30  to    4 :  30,  quiescence. 

Interruption 
9:15  to  10:00,  22  strong  contractions. 
10:00  to  II :  ID,  fairly  quiescent. 
1 1 :  10  to  1 1 :  50,  continuous  feeble  contractions. 
11:50  to  12:30,  36  strong  contractions. 
July  I.     A.M.     12:30  to  12:40,  quiescence. 

12 :  40  to    1 :  20,  continuous  feeble  contractions. 
1 :  20  to    2 :  25,  45  strong  contractions. 
2 :  25  to    2 :  50,  continuous  feeble  contractions. 
2:50  to    3:30,  27  strong  contractions. 
3 :  30  to    4 :  00,  quiescence. 
4:00  to    4:30,  continuous  feeble  contractions. 
4 :  30  to    5 :  20,  26  strong  contractions. 

Interruption 
8:45  to    9:5s,  43  strong  contractions. 
10:20  to  12:20,  contractions  all  the  time,  but  feeble. 
P.M.     12:20  to    1:00,  19  strong  contractions. 
Interruption 
3 :  45  to    4 :  00,  20  fairly  strong  contractions. 

Interruption 
8:35  to    9:25,  37  strong  contractions. 
9:25  to  11:20,  continuous,  fairly  strong  contractions. 
II :  20  to  12 :  25,  47  very  strong  contractions. 
July  2.    A.M.     12:25  to  12:50,  fairly  quiescent. 

12:50  to    2:35,  continuous,  fairly  strong  contractions  (60). 
2:35  to    3:30,  fairly  quiescent. 

3:30  to    4:50,70    strong    contractions,    ending    in    tetanus 
(4  min.). 
Interruption 
6 :  30  to    7 :  40,  quiescence. 
7 :  40  to    8 :  40,  2)2>  strong  contractions. 

Interruption 
10:25  to  11:15,  29  strong  contractions. 
Interruption 
P.M.       1 :  00  to    3  :oo,  continuous,  fairly  strong  contractions,  stronger 
toward  the  end. 
Interruption 


128        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

July  2.    P.M.       8:45  to    9:00,  22  strong  contractions. 

9 :  GO  to    9 :  50,  continuous  feeble  contractions. 
9:50  to  10:30,  27  strong  contractions. 
10:30  to  11:30,  continuous,  fairly  strong  contractions. 
I         1 1 :  30  to  1 2 :  30,  34  strong  contractions. 
July  3.     A.M.     12:30  to    2:25,  continuous,  fairly  strong  contractions. 

2:25  to    3:40,  60  strong  contractions,  ending  in  incomplete 

tetanus  (5  min.). 
3:40  to    4:05,  continuous  feeble  contractions. 
4:05  to    5:00,  42  strong  contractions. 

Interruption 
8:30  to    9:25,  30  strong  (not  maximum)  contractions. 
11:25  to    1:00,  continuous,  fairly  strong  contractions. 
1 :  00  to    1 :  40,  30  strong  contractions. 

Interruption 
4:45  to    5:15,  continuous  feeble  contractions. 
9:00  to    9:45,  38  strong  contractions. 
9:45  to  1 1 :  20,  continuous  feeble  contractions. 
11:20  to  12:10,  39  strong  contractions. 
July  4.    A.M.     12: 10  to    1 :  10,  continuous  feeble  contractions. 
1 :  10  to    2:35,  60  strong  contractions. 
2 : 3  5  to    3 :  40,  fairly  quiescent . 
3 :  40  to    5 :  40,  50  strong  contractions. 
End  of  experiment:  Body  weight,  69.8  kg.    Loss  of  body  weight,  4.2  kg. 

Confming  our  attention  for  the  present  to  the  objective  phe- 
nomena, i.e.,  the  gastric  tonus  and  the  hunger  contractions,  we 
find  the  following  facts  to  be  apparent : 

1.  There  is  no  decrease  in  the  gastric  tonus  and  the  hunger 
contractions,  but,  on  the  contrary,  an  increase,  especially  in  the 
tonus,  and  in  the  frequency  of  the  hunger  periods.  An  increase  in 
the  intensity  of  the  hunger  contractions  is  also  evidenced  in  the 
appearance  of  the  incomplete  hunger  tetanus  on  the  fourth  and 
fifth  days  of  starvation. 

2.  There  was  a  continuous  but  probably  scanty  secretion  of 
gastric  juice  during  the  entire  hunger  period,  as  the  balloon  on 
being  withdrawn  from  the  stomach  always  tasted  acid  and  gave 
the  acid  reactions. 

The  five  days'  hunger  period  of  Mr.  J.  H.  L.  began  on  July  14 
and  was  -concluded  on  July   19.    During  July   10   to    14  daily 


HUNGER  IN  PROLONGED  STARVATION  129 

observations  were  made  of  the  gastric  hunger  contractions,  in  order 
to  estabhsh  the  normal  frequency  and  general  character  of  these 
contractions  in  Mr.  L.  The  periods  of  hunger  contractions  of 
Mr.  L.  under  normal  conditions  of  eating  differ  from  those  of  the 
writer  by  usually  ending  in  the  incomplete  tetanus  previously 
described  in  Mr.  V.  This  is  probably  due  to  the  fact  that  Mr.  L. 
is  sixteen  years  younger  than  the  writer. 

Summary  of  the  Observations  on  Mr.  J.  H.  L. 
Control  Period 

July  10.  No  breakfast  or  lunch;  1:30  to  4:25  p.m.,  period  of  observation; 
2:00  to  2:40  P.M.,  gradually  increasing  contractions  ending  in  11  strong 
contractions  and  strong  tetanus  (3^  min.).  Feeble  rapid  contractions 
began  to  reappear  at  3 :  15  and  gradually  increased  in  amplitude. 

July  II.  No  breakfast;  9:00  a.m.  to  12:00  p.m.,  continuous  fairly  strong 
contractions.  Period  of  15  strong  contractions;  10:30  to  11:00  a.m.  and 
11:00  a.m.  to  12:00  M.,  continuous  fairly  strong  contractions  (22  con- 
tractions) . 

July  12.  No  breakfast;  9:35  to  10:10  a.m.,  22  contractions  of  gradually 
increasing  strength  in  30  minutes,  ending  in  3-minute  incomplete  tetanus. 

July  13.  No  lunch;  12:00  to  12:30  p.m.,  continuous,  fairly  strong  contrac- 
tions. A  small  group  (10)  of  strong  contractions  12:30  to  12:45  P-^-  A 
period  of  strong  contractions  (22  gradually  increasing  ending  in  3-minute 
tetanus)  i :  50  to  2 :  30  p.m. 

July  14.  10:00  A.M.  to  1:00  P.M.  No  breakfast;  10:00  to  10:50  a.m.,  31 
gradually  increasing  strong  contractions  ending  in  tetanus  (2  min.); 
1 1 :  30  A.M.  to  1 2 :  00  M.,  14  fairly  strong  contractions,  no  tetanus;  1 2 :  30  to 
I  :oo  P.M.,  21  gradually  increasing  strong  contractions  ending  in  a  3-minute 
tetanus. 

Fasting  Period 

Last  meal,  July  14,  2:00  p.m.    Body  weight,  62.8  kg. 
July  15.    P.M.     7:45  to    8:25,  19  fairly  strong  contractions. 
8:25  to    8:35,  quiescence. 
8:35  to    9:00,  28  fairly  strong  contractions. 
9 :  00  to    9:15,  quiescence . 

9: 15  to    9:45,  period  of  21  fairly  strong  contractions. 
9:45  to    9:55,  quiescence. 

9:55  to  10:25,  period  of  21  fairly  strong  contractions. 
10: 25  to  II  :oo,  period  of  18  fairly  strong  contractions. 
11:05  to  11:40,  period  of  17  fairly  strong  contractions. 
Interruption 


Fig.  15 


Fig.  15. — I.  Records  of  the  contractions  of  the  empty  stomach  of  A.  J.  C.  Bromo- 
form  manometer.  A ,  final  ten  minutes  of  a  typical  period  of  hunger  contractions  ten 
hours  after  a  meal;  B,  final  after  ten  minutes  of  a  typical  hunger  period  after 
five  days'  starvation.  Note  in  tracing  B  the  prolonged  period  of  incomplete  tetanus 
at  the  culmination  of  the  hunger  period,  and  the  reappearance  of  a  feeble  20-seconds 
rhythm  immediately  following  the  cessation  of  the  period  of  strong  hunger  con- 
tractions. Showing  the  increase  in  the  tonus  and  the  hunger  contractions  of  the 
empty  stomach  during  prolonged  starvation.    Four-ninths  original  size. 

II,  Typical  record  (10  minutes)  of  the  hunger  contractions  of  the  stomach  of 
dogs.  A ,  after  8  days'  starvation;  B,  after  ten  days'  starvation;  showing  a  persistence 
of  the  gastric  hunger  contractions  during  prolonged  starvation.  C,  tracing  showing 
end  of  a  gastric  hunger  period  of  a  dog  after  6  days'  starvation.  The  vagi  and  splanch- 
nic nerves  sectioned  before  the  starvation  period.    About  one-half  original  size. 


132        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

July  i6.    A.M.     9: 20  to  10: 25,  period  of  gradually  increasing  very  strong  con- 
tractions iss)}  ending  in  tetanus  (2  min.). 
InterrupHon 
P.M.     1 :  00  to    1 :  40,  period  of  gradually  increasing  strong  contrac- 
tions (25),  ending  in  tetanus  (3  min.). 
Interruption 
3-55^0    5:00,  quiescence. 
5:00  to    5:50,  period  of  fairly  strong  contractions  (17).    No 

tetanus. 
8 : 35  to    9:35,  period  of  very  strong  contractions  (37),  ending 

in  3 -minute  tetanus. 
9:35  to  10:20,  quiescence. 

10: 20  to  II :  20,  continuous,  fairly  strong  contractions. 
1 1 :  20  to  1 1 :  30,  fairly  quiescent. 

11:30  to  12:00,  period  of  fairly  strong  contractions  (11).    No 
tetanus. 
July  17.    A.M.  12:00  to  12:40,  continuous  feeble  contractions. 
1 2 :  40.  to    1 :  30,  quiescence. 
1 :  30  to    2 :  00,  continuous  feeble  contractions. 
2 :  00  to    3 :  00,  quiescence. 
3 :  00  to    5 :  30,  continuous  feeble  to  fairly  strong  contractions. 

Interruption 
9: 30  to  10: 10,  period  of  very  strong,  gradually  increasing  con- 
tractions   (36),    ending   in    tetanus   of    2^ 
minutes. 
Interruption 
P.M.  12:15  to    3 :  30,  practically  continuous,  feeble  to  moderately 
strong  and  strong  contractions. 
Interruption 
8:40  to  10:00,  continuous  feeble  to  moderately  strong  con- 
tractions. 
10:00  to  10:40,  period  of  very  strong,   gradually  increasing 
contractions  (20),  ending  in  tetanus  (2  min.). 
10:40  to  11:00,  quiescence. 

11:00  to  11:50,  period  of  moderately  strong  contractions  (23). 
No  tetanus. 
July  18.     A.M.  11:50  to    2:30,  mainly  quiescent  (occasional  feeble  contrac- 
tions). 
2 :  30  to    3 :  30,  period  of  very  strong,   gradually  increasing 

contractions  (34).    No  tetanus. 
3:30  to    4:00,  fairly   quiescent    (occasional   feeble   contrac- 
tions). 


HUNGER  IN  PROLONGED  STARVATION  133 

July  18.    A.M.    4:00  to    5:00,  period  of  strong,  gradually  increasing  contrac- 
tions (24),  ending  in  tetanus  (2§  min.). 
5:00  to    5:4s,  continuous  feeble  contractions. 

Interruption 
9: 20  to  10: 10,  period  of  fairly  strong  contractions  (35).    No 

tetanus. 
10:10  to  11:15,  fairly  quiescent. 

11:15  to  12:00,  period    of    strong    contractions    (22).      No 
tetanus. 
Interruption 
P.M.     2 :  30  to    3 :  50,  continuous,  very  feeble  contractions. 
3:50  to    4:05,  period  of  10  fairly  strong  contractions. 
4:05  to    4:15,  quiescence. 
4:15  to    4:40,  period  of  13  strong  contractions. 
4 :  40  to    4 :  50,  quiescence. 

4: 50  to    5 :  30,  period  of  very  strong  contractions  (22),  ending 
in  tetanus. 
Interruption 
8:35  to    9:20,  32  strong  contractions,  practically  continuous. 

Strong  tonus. 
9:20  to  10:00,  continuous  feeble  contractions. 
10:00  to  10:50,  15  strong  contractions  (long  drawn  out).    One 

tetanus  period. 
10:50  to  11:30,  period  of  strong  contractions  (22),  ending  in 

very  strong  tetanus  (3  min.). 
11:30  to  12:40,  fairly  quiescent,  but  a  few  fairly  strong  con- 
tractions. 
July  19.  A.M.     12:40  to    1:25,  period  of  very  strong  contractions  (37).    No 

tetanus. 
1 :  25  to  1 :  45,  quiescence. 
1:45  to    2:15,  period  of  fairly  strong  contractions  (11).    No 

tetanus. 
2 : 1 5  to  2 :  30,  quiescence. 
2 :  30  to    3 :  10,  period  of  very  strong  contractions  (22),  ending 

in  a  3 -minute  tetanus. 
3 :  10  to    4:00,  continuous  very  feeble  contractions. 
4:15  to    6:00,  continuous  strong  contractions  (36),  ending  in 
tetanus    (3    min.).      (Long    and    irregular 
pauses  evidently  due  to  psychic  inhibition, 
as  Mr.  L.  was  very  restless.) 
End  of  experiment:  Body  weight,  59  kg.    Loss  of  body  weight,  3.8  kg. 

It  is  clear  that  the  results  on  Mr.  L.  practically  duplicate  those 
on  the  writer,     (i)  There  is  no  decrease,  but,  on  the  contrary,  an 


134        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

increase  in  the  gastric  tonus  and  in  the  hunger  contractions.  (2) 
The  stomach  showed  an  acid  reaction  all  the  time  during  the 
hunger  period,  evidently  due  to  a  continuous  but  scanty  secretion 
of  gastric  juice. 

2.      THE   SUBJECTIVE  PHENOMENA 

1.  General  condition. — Mr.  L.,  as  well  as  the  writer,  continued 
in  good  health  and  in  fairly  good  spirit  throughout  the  starvation 
period.  On  the  fourth  and  fifth  days  both  men  felt  somewhat 
weak.  Some  mental  depression  was  also  experienced,  especially 
on  the  fifth  day,  by  Mr.  L.,  who  complained  of  feeling  dizzy  on 
getting  on  his  feet  after  lying  down.  An  hour's  lecturing  seemed 
quite  an  effort  on  the  fourth  starvation  day,  and  on  the  fifth  day 
both  men  felt  distinctly  better  when  lying  down  than  when  sitting 
or  standing.  Both  slept  fairly  well  during  the  four  nights  of  the 
starvation  period,  despite  the  persistent  hunger  contractions  and 
the  unusual  surroundings  of  the  research  laboratory  as  a  sleeping- 
room.  The  secretion  of  urine  was  diminished,  although  water  was 
taken  whenever  desired.  In  some  cases  a  glass  of  water  was  taken 
to  diminish  the  hunger  pangs.  The  writer  did  not  enjoy  a  cigar 
after  the  second  day;  in  fact,  smoking  tended  to  produce  nausea. 
This  is  an  indication  of  increased  excitability  of  the  nerves  of  the 
gastero-intestinal  canal. 

2.  The  sensations  of  hunger  and  appetite. — During  the  period  of 
control  observations  both  subjects  trained  themselves  in  judging 
the  relative  intensity  of  the  individual  hunger  pangs,  and  in  this 
both  of  them  attained  a  fair  degree  of  efficiency.  They  can  invari- 
ably tell  the  onset  of  a  hunger  period  before  the  contractions  have 
reached  a  sufficient  intensity  to  be  recognized  as  individual  hunger 
pangs.  This  initiation  of  the  hunger  period  consists  in  a  gradually 
increasing  tonus  and  feeble  and  more  or  less  rhythmical  contrac- 
tions, and  this  is  felt  as  a  continuous  mild  hunger  or  a  moderately 
steady  and  somewhat  uncomfortable  tension  in  the  epigastric 
region.  This  sensation  is  not  dependent  on  or  influenced  by  the 
distended  balloon  in  the  stomach  cavity.  In  this  way  one  can 
usually  manage  to  record  practically  every  hunger  period  during 
the  day,  simply  by  starting  observations  as  soon  as  one  feels  the 


HUNGER  IN  PROLONGED  STARVATION  135 

very  onset  of  the  hunger  period.  The  periods  of  strongest  hunger  con- 
tractions, or  the  hunger  tetanus,  are  also  felt  as  continuous  and 
intense  hunger.  And  there  is  a  characteristic  relief  from  the 
diminished  tension  within  a  minute  or  so  after  the  period  of  hunger 
contractions  is  at  an  end. 

During  the  first  two  or  three  days  the  hunger  sensations  seemed 
both  to  Mr.  L.  and  the  writer  somewhat  more  severe  than  any 
hunger  experienced  during  the  control  period,  in  fact,  more  severe 
than  seemed  warranted  from  the  degree  of  intensity  of  the  gastric 
contractions.  To  be  sure,  the  hunger  contractions  of  the  stomach 
were  usually  somewhat  stronger  than,  and  in  every  case  at  least 
as  strong  as,  during  the  control  period,  but  the  hunger  sensations 
seemed  even  stronger  proportionately.  During  the  fourth  and* 
the  fifth  hunger  days,  on  the  other  hand,  the  hunger  sensation 
seemed  somewhat  weaker  than  one  could  have  predicted  from 
the  intensity  of  the  hunger  contractions.  In  fact,  the  sensation 
did  not  even  seem  to  be  as  keen  as  that  produced  by  a  period  of 
strong  hunger  contractions  6  to  10  hours  after  the  previous  meal. 
The  reader  will  recall  that  the  gastric  hunger  contractions  on  the 
last  two  days  were'  of  normal  or  greater  than  normal  intensity. 

The  sensation  of  hunger  was  almost  continuous  after  the  first 
day  of  starvation.  That  is  to  say,  the  hunger  sensation  referred 
to  the  epigastrium  did  not  wholly  disappear  during  the  intervals 
between  the  vigorous  gastric  contractions.  This  feeble  but  con- 
tinuous hunger  sensation  is  evidently  caused  by  the  increased 
gastric  tonus  and  more  or  less  continuous  but  feeble  rhythmical 
contractions  that  represent  the  periods  of  quiescence  of  the  empty 
stomach  during  prolonged  starvation.  On  the  fifth  day  of  starva- 
tion the  continuous  hunger  sensation  seemed  to  be  tinged  with  a 
peculiar  ''burning"  sensation,  also  referred  to  the  stomach,  the 
fusion  resembling  somewhat  the  feeling  of  "sick  stomach"  with 
its  attendant  central  depression.  This  "burning"  sensation  was 
probably  caused  by  acid  stimulation  of  hyperexci table  nerve-endings 
in  the  gastric  mucosa. 

The  appetite  during  the  starvation  period  ran  practically  par- 
allel with  the  sensation  of  hunger.     It  was  distinctly  increased 


136        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

during  the  first  two  or  three  days,  and  diminished  on  the  fourth 
and  fifth  days.  In  fact,  the  depression  of  appetite  on  these  two 
days  seemed  distinctly  greater  than  the  depression  of  the  hunger 
sensation.  Instead  of  an  eagerness  for  food,  there  was  almost  an 
indifference  toward  food,  despite  the  persistent  hunger  call  of  the 
empty  stomach.  This  was  particularly  true  of  Mr.  L.  He  stated 
several  times  on  the  fourth  and  fifth  days  that  the  sight  of  food 
led,  not  to  a  feeling  of  eagerness  for  eating,  but  to  a  feeling  par- 
taking of  the  nature  of  revulsion  or  nausea.  This  was  not  experi- 
enced by  the  writer.  Food  looked  good  to  him  throughout  the 
starvation  period,  but  he  found  it  much  easier  to  dismiss  thoughts 
of  food  and  eating  from  his  mind  toward  the  end  than  at  the 
beginning  of  the  period. 

The  reasons  for  this  seeming  discrepancy  in  the  parallel  between 
the  intensity  of  gastric  hunger  contractions  and  the  intensity  of 
the  subjective  hunger  sensation  during  the  five  days'  hunger  period 
can  only  be  conjectured,  at  present.  We  are  inclined  to  believe 
with  Stohr  that  the  weakening  of  the  hunger  and  the  appetite 
sensations  toward  the  end  of  the  period  is  due  to  a  depression 
of  the  central  nervous  system.  This  central  depression,  how- 
ever caused,  was  clearly  in  evidence  both  in  Mr.  L.  and  the 
writer.  Afferent  impulses  from  the  viscera,  differing  from  the 
normal  quantitatively,  probably  also  play  a  part  in  the  situa- 
tion. 

More  prolonged  starvation  in  man  appears  to  lead  at  times 
to  a  heightened  or  abnormal  cerebral  activity,  as  shown  by  the 
feeling  of  exaltation,  visual  and  auditory  hallucinations,  etc.  These 
phenomena  are  probably  determined  quite  as  much  by  the  type  of 
emotional  processes  of  the  individual  as  by  the  effects  of  starvation, 
since  they  are  reported  more  frequently  by  religious  ascetics,  than 
by  worldly  minded  men  starving  for  purposes  of  science  or  health. 
The  hallucinations  may  be  due  to  depression  of  certain  cerebral 
centers,  and  hence  similar  to  dreaming  rather  than  to  actual 
increase  in  cerebral  excitabihty.  In  any  case,  these  phenomena 
are  probably  due  to  starvation  changes  in  the  blood  and  the  brain 
tissues,  rather  than  to  the  gastric  hunger  mechanism. 


HUNGER  IN  PROLONGED  STARVATION  137 

3.  After-effects  of  the  starving  period. — Both  in  Mr.  L.  and  the 
writer  practically  all  of  the  mental  depression  and  some  of  the  feeling 
of  weakness  disappeared  during  the  partaking  of  the  first  meal  after 
the  fasting  period.  This  central  depression  is  therefore  essentially 
a  reflex  condition  depending  probably  on  afferent  impulses  from 
the  digestive  tract,  rather  than  a  result  of  lack  of  nutrient  material 
in  the  blood.  But  complete  recovery  from  the  bodily  weakness 
did  not  take  place  until  the  second  or  third  day  after  breaking 
the  fast. 

From  the  second  day  on  both  men  felt  unusually  well,  distinctly 
better,  in  fact,  than  before  the  hunger  period,  although  both  men 
are  normally  in  good  health  and  vigor  and  not  hampered  by  exces- 
sive fat.  The  writer  felt  as  if  he  had  had  a  month's  vacation  in 
the  mountains.  The  mind  was  unusually  clear  and  a  larger  amount 
of  mental  and  physical  work  was  accomplished  without  fatigue. 
In  the  writer's  own  case,  the  five  days'  starvation  period  increased 
the  vigor  of  the  gastric  hunger  contractions  to  that  of  a  young 
man  of  twenty  or  twenty-five,  and  the  empty  stomach  retained 
this  increased  vigor  for  at  least  three  weeks  after  the  hunger  period, 
when  observations  were  discontinued  owing  to  absence  from  the 
University.  This  improvement  or  rejuvenation  of  the  stomach 
is  not  a  matter  of  subjective  feeling  of  opinion,  but  a  matter  of 
objective  record  on  the  tracings.  Neither  Mr.  L.  nor  the  writer 
can  be  considered  as  ordinarily  eating  to  excess,  although  the  daily 
intake  of  protein  and  calories  is  greater  than  the  minimum  require- 
ment advocated  by  Chittenden.  The  cause  of  the  improvement 
was  not  loss  of  excessive  adipose  tissue. 

Mr.  L.  states  that  the  augmentation  of  hunger  and  appetite 
persisted  for  at  least  two  or  three  weeks  after  the  end  of  the  starva- 
tion period. 

We  are  familiar  with  but  not  particularly  impressed  by  the 
arguments  of  enthusiasts  who  advocate  starvation  as  a  panacea 
for  various  human  ills.  But  this  personal  experience  leads  us  to 
suspect  that  there  is  more  value  in  some  of  these  measures  than  is 
ordinarily  considered.  Civilized  man  has  traveled  far  from  the 
conditions  of  life  among  wild  animals  and  primitive  man,  with 


138        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

whom  periods  of  starvation  are  not  uncommon.  Occasional 
periods  of  starvation,  say  once  or  twice  a  year,  in  the  case  of 
healthy  adult  persons  may  not  only  add  to  the  joy  of  living  but 
also  to  the  length  of  life.  There  is  some  evidence  resulting  from 
experiments  with  animals  that  periods  of  starvation  may  accelerate 
growth  and  improve  the  general  body  metaboKsm  (Deland, 
McCollum,  Howe,  MorguHs). 

4.  Discomforts  of  starvation. — During  the  entire  starvation 
period  the  hunger  sensation  was  strong  enough  to  cause  some 
discomfort,  but  not  to  a  degree  that  could  be  called  marked  pain  or 
suffering.  This  discomfort  was  at  no  time  sufficient  to  interfere 
seriously  with  work.  And  since  practically  all  observers  agree 
that  the  hunger  discomfort  is  greatest  during  the  first  few  days 
of  starvation,  it  seems  probable  that  our  five  days  of  starvation 
gave  us  a  taste  of  the  maximum  discomfort  that  would  be  experi- 
enced in  more  protracted  fasts.  Accounts  of  acute  sufferings  from 
mere  starvation  (water  being  at  all  times  available)  must  therefore 
be  wholly  imaginary,  or  the  result  of  fear  and  panic.  Voluntary 
starvation  is  in  no  sense  a  heroic  act,  and  citation  of  hunger  experi- 
ments on  animals  in  the  interest  of  science  as  instances  of  cruelty 
to  animals  is  without  foundation. 

II.    RESULTS    ON   NORMAL  DOGS 

No  attempt  was  made  to  take  continuous  records  of  the  motor 
activity  of  the  empty  stomach  in  the  starving  dogs.  Observations 
were  made  for  periods  of  2  to  6  hours  each  day,  beginning  the 
second  or  third  day  of  starvation.  The  result  on  the  five  normal 
dogs  can  be  seen  at  a  glance  from  the  following  summary: 

Dog  I. — ^Young  Vigorous  Female 
Starvation  Day: 

2d  day.     10:25   A.M.   to   12:00  M.,   continuous  vigorous  contractions; 

type  II  and  III. 
3d  day.     2:00  to  4:00  P.M.,  continuous  vigorous  contractions,  type  II 

mainly. 
4th day.    10:25  A.M.  to  12:35  i*-M^->  continuous  contractions,  type  II 
mainly. 


HUNGER  IN  PROLONGED  STARVATION  139 

5th  day.    1 :  30  to  3 130  p.m.,  continuous  contractions,  type  II  mainly. 
6th  day.    10:55  a.m.  to  1:00  p.m.,  continuous  contractions,  type  III 

mainly. 
7th  day.    9 :  00  a.m.  to  i  2 :  00  m.,  continuous  contractions,  type  III  mainly. 
8th  day.    9:35  to  11 135  a.m.,  continuous  contractions,  type  II  mainly. 
9th  day.    10:35  A.M.  to  12:35  P-M.  continuous  contractions,  type   III 

mainly, 
loth  day.    9:35  a.m.  to  3 :  35  p.m.,  very  vigorous  contractions,  types  II  and 

III  only.    Tonus  on  the  average,  12  cm.  bromoform. 
End  of  experiment 

Dog  II. — Young  Vigorous  Female 

3d  day.  10:00  A.M.  to  3:00  P.M.,  strong  tonus  and  continuous  contrac- 
tions of  type  III. 

4th  day.  10:12  A.M.,  strong  tonus  and  continuous  contractions  of  type 
III. 

5th  day.     1:00  to  3:00  P.M.,  strong  tonus  and  continuous  contractions. 

6th  day.     9:00  a.m.  to  12:00  m.,  strong  and  continuous  contractions. 
Tonus  about  10  cm.  bromoform. 
End  of  experiment 

Dog  III.— Old  Female 

2d    day.     10:00  A.M.  to  i2:ooM.,  feeble  contractions,  type  I. 

3d  day.  9:00  to  II  :oo  a.m.,  a  few  irregular  contractions,  type  I;  stom- 
ach hypotonic. 

4th  day.  1 :  00  to  3 :  00  p.m.  ,  a  few  irregular  contractions,  type  I ;  stomach 
hypotonic. 

5th  day.  8:00  to  11:00  A.M.,  practically  no  contractions;  stomach 
hypotonic. 

6th  day.  1:00  to  4:00  p.m.,  practically  no  contractions;  stomach 
hypotonic. 

End  of  experiment 

Dog  IV. — ^Young  Vigorous  Female 

3d  day.  9:30  to  11:30  A.M.,  strong  tonus,  continuous  contractions, 
types  II  and  III. 

4th  day.  I  :oo  to  3  :oo  p.m.,  fairly  strong  tonus,  types  I  and  II  contrac- 
tions. 

5th  day.    8 :  00  to  1 1 :  00  a.m.,  strong  tonus,  types  II  and  III  contractions* 

7th  day.  9:40  A.M.  to  12:00  M.,  fairly  strong  tonus,  type  III  contrac- 
tions. 

8th  day.     i :  00  to  3 :  00  p.m.,  very  strong  tonus,  type  III  contractions. 


I40        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

9th  day.    8:00  to  10:00  A.M.,  feeble  tonus,  feeble  contractions,  type  II. 
loth  day.    8:00  to  11:00  a.m.,  fairly  strong  tonus;   fairly  strong  type  II 
contractions. 

End  of  experiment 

Dog.  v.— Six-Months-Old  Female 

2d  day.  Fast  30  hours;  type  II  contractions;  tonus  3  to  4  cm.    Chloro^ 
form. 

3d  day.  Type  II  contractions;  tonus  3  to  4I  cm. 

4th  day.  Type  II  contractions;  tonus  3  to  4!  cm. 

5th  day.  Type  II  contrdctions;  tonus  3  to  4I  cm. 

6th  day.  Types  II  and  III  contractions;  tonus  3  to  4!  cm. 

7th  day.  Types  II  and  III  contractions;  tonus  3  to  4I  cm. 

8th  day.  Types  II  and  III  contractions;  tonus  3  to  s\  cm. 

9th  day.  Types  II  and  III  contractions;  tonus  3  to  6j  cm. 

loth  day.  Type  III  contractions;  tonus  3  to  7  cm. 

nth  day.  Type  III  contractions;  tonus  3  to  6|  cm. 

12th  day.  Type  III  contractions;  tonus  3  to  6^  cm. 

13th  day.  Type  III  contractions;  tonus  3  to  6jcm. 

14th  day.  Type  II  and  prolonged  type  III  contractions;  tonus  3  to  7  cm. 

15th  day.  Type  III  contractions;  tonus  3  to  6\  cm. 

1 6th  day.  Six  hours  before  death  from  starvation;  type  II  and  prolonged 
type  III  contractions;  tonus  3  to  g\  cm. 

Dogs  I,  II,  and  IV  exhibited  either  normal  or  greater  than 
normal  hunger  contractions  of  the  empty  stomach  during  the 
entire  starvation  period.  The  increased  tonus  of  the  stomach  was 
particularly  marked.  In  consequence  of  this  increased  tonus  the 
types  of  hunger  contractions  were  usually  those  previously  de- 
scribed as  II  and  III,  that  is,  practically  incomplete  tetanus. 
Judging  from  observations  on  man,  the  dogs  probably  felt  con- 
tinuous and  intense  hunger  during  these  contractions. 

The  only  old  dog  in  this  series,  No.  Ill,  had  shown  rather  feeble 
and  irregular  gastric  hunger  contractions  before  the  starvation 
period.  The  reason  for  this  was  not  apparent.  The  dog  was  in 
good  condition  and  would  eat  greedily,  even  when  the  empty 
stomach  was  practically  quiescent  and  distinctly  hypotonic.  This 
dog  showed  virtually  no  gastric  hunger  contractions  after  the  third 
day  of  starvation,  and  the  stomach  appeared  distinctly  hypotonic. 
The  dog  was  eager  for  food,  however. 


HUNGER  IN  PROLONGED  STARVATION 


I4t 


The  stomach  of  the  dogs  showed  acid  reaction  throughout  the 
hunger  period,  just  as  was  the  case  with  the  stomachs  of  the 
starving  men. 

It  will  thus  be  seen  that  the  empty  stomach  of  men  and  dogs 
exhibits  ordinarily  either  normal  or  greater  than  normal  himger 
contractions  during  starvation  periods  of  from  5  to  15  days. 

The  cause  of  this  increased  hunger  activity  of  'the  stomach 
may  be:  (i)  an  increase  in  the  tonus  innervation  via  the  vagi; 
(2)  changes  in  the  blood  in  consequence  of  starvation;  (3)  starva- 
tion metabolism  of  the  motor  tissues  of  the  stomach  itself. 


1    , 

111      1       1   1   1   a                  f 

u  DntiQt/t 

1              ^j?"*>tliQJ>'"^r' 

J' 

i;j>iiii±i?^ 

Fig.  16. — Diagrammatic  representation  of  the  amplitude  of  a  gastric  hmiger 
contraction  on  the  base  of  the  rising  tonus  as  constructed  from  the  daily  tracings 
during  starvation  of  a  young  dog.  Each  of  the  above  squares  represents  i  sq.  cm. 
The  erect  pyramids  indicate  the  amplitudes  of  the  hunger  contractions  in  centimeters 
arranged  on  the  rising  tonus  as  a  base  line.  Spaces  left  to  right  indicate  number  of 
days  of  starvation;  spaces  from  bottom  to  top  daily  increase  in  the  gastric  tonus  in 
centimeters.  Note  the  rapid  increase  in  gastric  tonus  and  decline  in  amplitude  of 
contractions  on  the  15  th  day  as  produced  by  the  prolonged  type  III  hunger  contractions 
(Patterson) . 


III.      EXPERIMENTS   ON  DOGS  WITH  THE   STOMACH  ISOLATED 
FROM   THE  CENTRAL  NERVOUS   SYSTEM 

In  order  to  decide  between  these  three  possibilities  starvation 
tests  were  m'ade  on  two  dogs  with  complete  isolation  of  the  stomach 
from  the  central  nervous  system  by  section  of  the  vagi  and  the 
splanchnic  nerves  and  on  one  dog  with  the  vagi  nerves  severed, 


142        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

the  splanchnic  nerve  being  left  intact.     The  following  is  a  brief 
summary  of  the  results: 

Dog  VL — Young  Female.    Section  of  the  Vagi  and  Splanchnic  Nerves 
Two  Weeks  before  Starvation  Period 
Starvation  Day: 

4th  day.     io:oo  a.m.  to  i:oo  p.m.,  one  group,  type  I  contractions  (15), 

fairly  strong. 
5th  day.     2:00  to  5:00  P.M.,  type  I  contractions,  fairly  strong  but  with 

long  intervening  pauses. 
6th  day.     10:00  a.m  to  12:00  m.,  30  strong  (type  I)  contractions  ending 

in  tetanus  (Fig.  5^). 
7th  day.     1:00  to  4:30  P.M.,  continuous  contractions  of  type  III;   tonus 
about  10  cm.  bromoform. 

End  of  experiment 

Dog  VII. — Adult  Fairly  Vigorous  Female.    Vagi  and  Splanchnic  Nerves  Cut 

5th  day.     9:00  to  11:00  A.M.,  9  very  vigorous  contractions  and  tetanus 

periods. 
6th  day.     1:00  to  3:00  p.m.,  fairly  strong  contractions  of  type  I;    long 

pauses  between  contractions. 
7th  day.     1:00  to  5:00  p.m.,  stomach  hypotonic;   no  contractions. 
End  of  experiment 

Dog  VIII. — Young,  Fairly  Vigorous  Female.    Vagi  Nerves  Sectioned 

3d   day.     9:00  to  11:00  A.M.,  fairly  strong  type  I  contractions. 

5th  day.     1:00  to  5:00  P.M.,  strong  (type  I)  contractions,  long  pauses 
between  contractions. 

6th  day.     9:00  to  11:00  a.m.,  stomach  hypotonic,  practically  no  contrac- 
tions. 

7th  day.     1:00  to  4:00  P.M.,  fairly  strong  type  I  contractions,  prolonged 
and  partly  tetanic;  long  pauses  between  contractions. 
End  of  experiment 

The  gastric  hunger  contractions  of  Dog  IV  were  absent  on  the 
seventh  day  of  starvation,  but  Dogs  V  and  VII  showed  either 
normal  or  greater  than  normal  hunger  contractions  throughout 
the  starvation  period.  Since  the  increase  in  the  hunger  contrac- 
tions appeared  to  be  just  as  marked  in  the  dogs  with  the  stomach 
isolated  from  the  central  nervous  system  as  in  normal  dogs,  it 
follows  that  the  cause  of  this  increase  is  not  an  augmentation  of 
the  vagus  tonus. 


HUNGER  IN  PROLONGED  STARVATION  143 

These  starvation  periods  were  not  of  sufficient  length  to  cause 
very  marked  asthenia  either  in  the  men  or  in  the  dogs  (except 
Dog  V).  They  do  show  that  the  hunger  tonus  and  contractions 
persist  with  normal  or  greater  than  normal  vigor  during  shorter 
starvation  periods.  Cases  of  gastric  hypo  tonus  and  decreased  gas- 
tric motility  cannot  therefore  be  due  to  starvation  as  such,  but  to 
some  special  and  exceptional  factors.  The  depression  may  be  due 
(i)  to  a  primary  asthenia  of  the  stomach;  (2)  to  central  inhibition 
via  the  splanchnic  nerves  (pains,  depressions,  etc.);  (3)  to  acid 
inhibition  from  the  stomach  mucosa  owing  to  copious  secretion  of 
gastric  juice.    This  question  requires  further  investigation. 

IV.      EXPERIMENTS    ON  DOGS   WITH   PANCREATIC   DIABETES 

It  is  w^ell  known  that  men  and  other  animals  afflicted  with 
diabetes  lose  weight  rapidly,  despite  greater  appetite  and  increased 
food  consumption.  In  the  last  stage  of  diabetes  in  dogs  the  animal 
shows  greater  emaciation  than  a  normal  dog  at  death  from  lack  of 
food.  Dr.  Luckhardt  studied  the  gastric  tonus  and  hunger  con- 
tractions in  two  diabetic  dogs,  and  found  them  persisting  and  even 
augmented  to  within  a  few  hours  of  death,  when  the  animal  is  too 
emaciated  and  feeble  to  stand,  or  to  masticate  and  swallow  food. 
It  is  true  that  death  from  diabetes  involves  factors  that  are  not 
present  in  the  normal  animal  dying  from  starvation,  but  dogs 
dying  from  pancreatic  deficiency  have  all  the  appearances  of  an 
animal  in  the  most  extreme  state  of  emaciation.  Nevertheless, 
there  is  no  gastric  atony,  and  the  animal  gives  evidence  of  hunger 
and  appetite  in  his  avidity  for  food  to  within  a  few  hours  of  death. 

V.      EXPERIMENTS   ON  RABBITS 

Rabbits  succumb  to  starvation  much  more  rapidly  than  does 
man  or  the  dog.  Rogers  found  no  indication  of  depression  or  rest 
in  the  continuous  gastric  hunger  contractions  of  the  starving  rabbit 
until  within  a  few  hours  of  death.  Then  they  became  weaker,  of 
shorter  duration,  and  may  alternate  with  periods  of  quiescence. 
Shortly  before  death  from  starvation  the  rabbit's  stomach  may 
go  into  periods  of  strong  tetanus,  or  spasms  lasting  even  for  two 


144        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

to  three  minutes.  Similar  periods  of  gastric  tetanus  were  observed 
by  Patterson  in  starving  dogs  shortly  before  death.  In  a  normal 
animal  these  tetanic  contractions  of  the  stomach  would  give  rise 
to  intense  hunger  pangs,  but  we  cannot  know  what  sensation,  if 
any,  they  produce  in  the  animal  in  extreme  starvation  since  we 
have  no  data  concerning  this  condition  in  man.     In  fact,  we  do 

not  even  know  the  motor  condition 
of  man's  stomach  near  death  from 
starvation. 

VI.      DISCUSSION  OF   RESULTS 

So  far  as  we  are  aware,  this  is 

the  first  time  that  actual  records 

have   been   taken   of    the    gastric 

hunger  contractions  in  man  during 

Fig.  i7.-Superimposed  life-size     prolonged  starvation;  and  also  the 

tracings  of  the  stomachs  of  two  adult     first   time    that   the   physiologists 

rabbits;   the  larger   represents  the     themselves  have  done  the  Starving. 

stomach  of  a  rabbit  killed  after  eat-      t.    ,  #  .        r  .  i 

ing;  the  smaller  the  stomach  of  a     ^^^  we  have  many  accounts  of  the 
rabbit  which  died  of  starvation,  but     subjective   feeling  of   hunger  and 
had  been  permitted  to  eat  its  own     appetite  in  man  during  long  fasts, 
eces  (  ogers;.  ^   comparison   of    these  accounts 

with  our  own  results  is  rendered  difficult  by  the  confusion  between 
the  sensations  of  hunger  and  of  appetite  that  unfortunately  obtains 
in  physiological  and  medical  literature.  Leaving  out  the  cases  com- 
plicated by  water  starvation,  there  appears  to  be  a  general  agreement 
that  the  sensations  of  hunger  and  appetite  increase  during  the  first 
few  (2  or  3)  days  of  starvation,  and  then  decrease  even  to  complete 
abolition.  Succi  reverted  to  drugs  to  deaden  the  hunger  pangs 
only  during  the  first  two  days  of  his  30-day  fast.  Viterbi,  who 
starved  himself  to  death  voluntarily  and  kept  a  daily  record  of  his 
feelings,  noted  complete  absence  of  hunger  after  the  fifth  day. 
Cetti  and  Breihaupt  did  not  experience  any  discomfort  from  hun- 
ger after  the  first  few  days,  but  it  is  not  clear  that  hunger  and 
appetite  were  altogether  lacking.  The  young  man  starving  for  5 
days  under  the  observation  of  Johansson,  Landergren,  Sonden  and 


HUNGER  IN  PROLONGED  STARVATION  145 

Tigerstedt  complained  of  weakness,  dizziness,  and  cold,  but  did 
not  feel  particularly  hungry  at  the  end  of  the  fast.  Carrington 
cites  many  cases  of  men  and  women  in  prolonged  starvation  where 
hunger  sensation  subsided  or  disappeared  after  the  third  day.  All 
these  persons  cited  by  the  last  author  were,  however,  suffering 
from  this,  that,  or  the  other  ailment,  and  some  of  them  were  lying 
in  bed  during  the  entire  starvation  period.  These  remarks  apply 
also  to  various  popular  accounts  of  cases  of  prolonged  fasting  to 
cure  digestive  or  nervous  disorders.  All  cases  of  compulsory  starva- 
tion (persons  shipwrecked,  explorers  and  hunters  lost,  or  cut  off 
from  supplies,  etc.)  are  usually  complicated  by  lack  of  water,  by 
the  effects  of  exposure,  and  by  fear,  panic,  etc.,  so  that  the  state 
of  the  actual  hunger  sensation  cannot  be  determined. 

In  the  case  of  the  31-day  fast  recently  reported  by  Benedict, 
the  subject,  a  man  forty  years  old,  having  had  previous  training 
in  long  fasts,  insisted  that  he  felt  no  hunger  at  any  time  during 
the  long  starvation.  Langfeld  thinks  that  this  might  have  been 
due  to  strong  auto-suggestion,  the  subject  being  a  vegetarian  and  a 
firm  believer  in  fasting  as  a  cure-all.  If  Benedict's  man  told  the 
truth,  there  must  have  been  some  abnormality  in  his  hunger 
mechanism,  or  else  he  was  able  to  shunt  the  visceral  hunger  impulses 
out  of  consciousness  by  hypnosis.  Polimanti  states  that  hunger 
can  be  induced  by  suggestion  or  hypnosis.  We  doubt  the  truth  of 
this  statement,  at  least  as  regards  the  real  gastric  hunger;  but  if  it 
is  true  it  is  probable  that  hypnosis  may  also  inhibit  the  hunger. 

All  these  accounts  are  based  on  the  statements  of  persons  who 
were  in  no  sense  trained  observers.  In  view  of  that  fact,  it  is 
probable  that  the  consensus  of  opinion  that  hunger  disappears 
after  the  third  day  of  starvation  means  no  more  than  that  after 
the  third  day  the  hunger  sensation  is  not  so  persistent  or  painful 
as  to  dominate  consciousness. 

There  was,  certainly,  some  decrease  in  the  hunger  and  especially 
in  the  appetite  sensation  of  the  writer,  and  of  Mr.  L.,  on  the  fourth 
and  fifth  days.  But  it  was  a  decrease,  not  an  absence  of  hunger 
sensation.  It  has  already  been  pointed  out  that  the  decrease  in 
intensity  of  the  hunger  sensation  was  not  due  to  a  decrease  in 


146        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

the  intensity  of  the  gastric  hunger  contractions,  but  to  depression 
of  the  central  nervous  system,  or  some  disturbance  in  the  complex  of 
impulses  from  proprioceptors.  We  do  not  deny  the  possibility  that 
the  sensation  of  hunger  may  actually  disappear  in  some  persons 
after  two  or  three  days  of  fasting,  but  this  is  not  due  to  starvation 
as  such,  but  to  special  conditions,  such  as  primary  asthenia  of 
the  stomach,  great  cerebral  depression,  inhibition  via  the  splanch- 
nic nerves  through  pain  or  other  factors  causing  hyperactivity  of 
the  sympathetic  system,  or  to  copious  and  continuous  secretion  of 
gastric  juice  causing  acid  inhibition.  In  view  of  our  results  on 
experimental  animals  it  seems  probable  that  during  periods  of 
prolonged  starvation  the  sensation  of  hunger  will  prove  most 
persistent  in  young  and  vigorous  persons. 

Boldyreff  states  that  the  periodic  contractions  of  the  empty 
stomach  in  dogs  become  feeble  and  irregular  during  prolonged 
fasting  and  cease  entirely  after  a  fast  of  3  to  4  days.  After  that  time 
there  is  a  copious  and  continuous  secretion  of  gastric  juice.  If  this 
spontaneous  secretion  of  gastric  juice  is  sufficiently  rapid,  there 
will,  of  course,  be  an  acid  inhibition  of  the  hunger  contractions. 

Only  one  of  our  dogs  (No.  Ill)  corroborates  the  results  of 
Boldyreff.  Dog  III  showed  practically  no  hunger  contractions 
after  the  third  day.  The  reader  will  recall  that  this  was  the  oldest 
dog  in  the  series,  and  that  he  had  shown  relatively  weak  and 
irregular  hunger  contractions  during  the  control  period  before 
starvation.  This  fact  probably  indicates  an  asthenic  condition 
of  the  stomach,  in  additioa  to  the  certain  factor  of  age. 

Boldyreif 's  dogs  had  duodenal,  biliary,  and  pancreatic  fistulae, 
in  addition  to  the  fistula  of  the  stomach.  As  these  animals  were 
thus  subjected  to  greater  disturbance  of  digestion  and  metabolism 
than  were  the  dogs  used  in  our  starvation  tests,  it  seems  probable 
that  the  dogs  used  by  Boldyreff  were  subnormal  in  respect  to 
some  asthenia  of  the  digestive  tract.  This  may  be  a  factor  in  the 
early  disappearance  of  gastric  hunger  contractions  during  the  pro- 
longed starvation.  Multiplication  of  fistulae  also  increases  the 
chances  for  reflex  inhibition  of  the  stomach  from  adhesions,  pain, 
etc.    While  the  difference  in  Boldyreff's  results  and  our  own  may 


HUNGER  IN  PROLONGED  STARVATION  147 

be  due  mainly  to  the  difference  in  the  condition  of  the  dogs  at  the 
beginning  of  the  hunger  tests,  it  may  also  be  noted  that  Boldyreff's 
method  of  registering  the  gastric  contractions  was  not  delicate 
enough  to  show  the  weaker  contractions  and  the  variations  in 
tonus.  The  strong  continuous  tonus  and  rapid  contractions  (type 
III)  which  we  have  designated  the  ''hunger  tetanus"  would  prob- 
ably not  have  been  recorded  on  Boldyreff's  tracings.  It  was 
precisely  this  hunger  tetanus  which  was  mostly  in  evidence  in  our 
normal  starving  dogs. 

Boldyreff  found  that  during  the  first  three  days  of  starvation 
there  are  periods  of  apparently  spontaneous  secretion  of  gastric 
juice,  and  that  during  this  secretion  the  gastric  contractions  ceased. 
After  the  third  day  the  gastric  secretion  became  continuous.  We 
did  not  subject  our  dogs  to  the  additional  inconvenience  of  accurate 
determination  of  the  rate  of  gastric  secretion,  but  incidental  obser- 
vations in  other  lines  of  work  on  cats  with  the  stomach  pouch  of 
Pavlov  have  convinced  us  that  there  may  be  considerable  fluctua- 
tion in  the  rate  of  the  secretion  of  the  empty  stomach.  The 
secretion  of  gastric  juice  must  be  relatively  rapid,  however,  in 
order  to  maintain  complete  inhibition  of  the  tonus  and  contractions 
of  the  healthy  and  vigorous  stomach  through  acid  stimulation  of 
local  and  long  reflexes.  The  stomach  of  the  writer,  of  Mr.  L.,  and 
of  all  the  dogs  was  acid  throughout  the  starvation  period,  which 
indicates  a  more  or  less  continuous  secretion  of  gastric  juice,  even 
during  the  first  three  days  of  starvation.  But  the  quantity  or 
strength  of  hydrochloric  acid  in  the  stomach  at  any  one  time  was 
not  sufficient  to  produce  the  acid  inhibition  either  in  man,  dog, 
or  rabbit. 

That  starvation  in  man  will  ultimately  lead  to  marked  weak- 
ening (and  eventually  absence)  of  the  sensation  of  hunger  owing  to 
the  depression  of  the  central  nervous  system  and  asthenia  of  the 
gastric  motor  mechanism  is  self-evident,  but  in  young  and  vigorous 
animals  this  depression  is  absent  until  the  skeletal  neuromuscular 
asthenia  is  very  marked.  That  prolonged  starvation  in  the  case 
of  healthy  individuals  should  completely  abolish  the  sensation  of 
hunger  and  appetite  while  the  organism  is  still  in  fair  state  of 


148        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

integrity  is  inherently  improbable.  When  it  does  occur,  it  is 
probably  due  to  pathological  complications.  Starvation  increases 
the  desire  for  food  (that  is,  hunger  and  appetite)  in  wild  animals, 
at  least  up  to  the  point  where  the  asthenia  reaches  a  degree  that 
renders  locomotion  impossible.  This  is  shown  by  the  increased 
boldness  and  disregard  of  danger  on  the  part  of  the  starving  animal 
(herbivorous  as  well  as  carnivorous)  in  his  search  for  food. 


CHAPTER  X 
THE  NERVOUS  CONTROL  OF  THE  HUNGER  MECHANISM 

The  question  of  the  nervous  control  of  the  gastric  hunger 
mechanism  embraces  several  important  physiological  problems, 
none  of  which  are  as  yet  completely  solved. 

1 .  On  the  motor  side  we  have  the  possibility  of  actual  initiation 
of  the  gastric  hunger  contractions  through  the  motor  fibers  in  the 
vagi  nerves  by  impulses  from  cerebral  as  well  as  lower  centers 
acting  on  the  motor  nuclei  of  the  vagi  in  the  medulla.  Even  if 
contractions  are  not  actually  caused  in  this  manner,  it  can  be  shown 
that  they  are  in  part  dependent  on  a  '^ tonus"  influence  exerted 
on  the  stomach  by  the  vagi  nerves.  Hence  the  control  of  the 
vagus  tonus  becomes  a  question  of  paramount  importance  in  the 
physiology  and  pathology  of  hunger. 

2.  On  the  afferent  or  sensory  side  we  must  determine  the  central 
paths  of  the  afferent  gastric  nerves  in  order  to  elucidate  the  genesis 
of  the  conscious  hunger  sensation  as  well  as  the  conscious  and 
subconscious  reflexes  evoked  by  these  afferent  impulses.  This 
raises  the  question  of  the  sensory  hunger  center  in  the  cerebrum. 

3.  We  have  also  to  deal  with  the  very  important  reflex  control 
of  the  gastric  hunger  mechanism  as  well  as  of  the  nervous  foci  in 
the  medulla^  mid-brain,  and  cerebrum  concerned  in  the  conduction 
of  sensory  and  motor  hunger  impulses. 

4.  And,  lastly,  we  must  consider  the  automatic  or  reflex, ele- 
ments in  the  gastric  hunger  mechanism  itself,  independent  of  all 
central  nervous  system  control.  An  understanding  of  these  several 
factors  is  of  particular  importance  for  the  interpretation  and  the  con- 
trol of  the  changes  in  hunger  and  appetite  that  we  meet  in  disease. 

I.   INFLUENCE  OF  THE  CEREBRUM 

I.  Efect  of  removal  of  the  cerebrum. — Removal  of  the  cerebral 
hemispheres  in  the  guinea-pig  leads  to  somewhat  increased  gastric 
tonus  and  hunger  contractions  (Dr.  King).    In  the  pigeon  this 

149 


I50        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

operation  does  not  change  the  hunger  contractions  of  the  empty 
crop,  except  that  visual  and  auditory  stimuH  do  not  lead  to  inhibi- 
tion of  these  movements  in  the  decerebrated  bird  (Rogers).  In 
frogs  removal  of  the  cerebrum  has  no  effect  on  the  hunger  con- 
tractions of  the  stomach  (Patterson).  Goltz's  decerebrated  dog 
showed  hunger.  We  may  therefore  conclude  that  in  so  far  as  the 
stomach  hunger  contractions  are  dependent  upon  tonus  and  motor 
nervous  impulses  via  the  vagi  nerves,  these  impulses  do  not 
originate  in  the  cerebral  hemispheres. 

2.  The  gastric  hunger  mechanism  during  sleep. — In  man  (infants 
as  well  as  adults)  the  gastric  hunger  contractions  are  at  least  as 
frequent  and  intense  during  sleep  at  night  as  during  the  waking 
state.  In  our  five  days'  starvation  experiment  continuous  records 
of  the  stomach  contractions  were  taken  during  sleep  at  night. 
These  records  show  that  the  stomach  was  in  strong  tonus  and 
hunger  contractions  practically  half  of  the  time  of  sleeping.  The 
hunger  periods  were  less  frequent  during  the  day  when  the  subject 
was  about  his  work. 

Numerous  experiments  on  dogs  show  that  the  hunger  contrac- 
tions and  the  gastric  tonus  are  more  vigorous  and  regular  when 
the  animal  is  sleeping  than  when  he  is  awake  and  taking  notice 
of  things  about  him.  The  only  apparent  exception  to  this  condition 
so  far  observed  in  any  species  is  the  rumen  of  the  goat.  A  few 
observations  on  one  goat  seemed  to  show  that  the  hunger  con- 
tractions of  the  rumen  or  first  stomach  pouch  decrease  in  intensity 
when  the  animal  is  lying  down  sleeping.  We  shall  not  be  satisfied 
that  this  is  so  until  the  same  result  is  obtained  on  a  number  of 
ruminants.  Possibly  the  gastric  motor  part  of  the  vagi  nervous 
apparatus  in  the  ruminating  animals  is  under  a  more  direct  control 
from  the  cerebrum  than  is  the  case  in  other  species. 

During  sleep  there  is  decreased  activity  of  the  central  nervous 
system  in  general;  decreased  tonus  of  the  skeletal  muscles;  de- 
creased tonus  of  the  musculature  of  the  blood  vessels,  at  least  in 
certain  parts  of  the  vascular  system;  decreased  tonus  of  the 
urinary  bladder,  etc.;  in  short,  a  lowered  activity  of  all  the  neuro- 
muscular mechanisms  so  far  investigated.     One  might  have  ex- 


NERVOUS  CONTROL  OF  THE  HUNGER  MECHANISM      151 

pected  that  so  far  as  the  tonus  of  the  empty  stomach  depends  on  a 
central  influence  by  way  of  the  vagi  the  gastric  tonus  and  hunger 
contractions  would  be  diminished  during  sleep.  But  instead  of 
being  depressed  in  sleep"  the  hunger  contractions  continue  with 
the  same  vigor  as  during  the  waking  state,  and  in  many  instances 
with  increased  vigor.  The  increase  in  the  gastric  hunger  con- 
tractions during  sleep  may  be  due  to  the  elimination  of  all  inhibi- 
tory impulses  via  the  splanchnic  nerves.  But  the  absence  of 
depression  certainly  indicates  that  the  vagogastric  tonus  mech- 
anism, at  least  in  man  and  dog,  occupies  a  unique  position  in  the 
organism — a  degree  of  independence  of  afferent  impulses  (extero- 
ceptors)  and  central  processes  not  known  in  the  case  of  any  other 
neuromuscular  apparatus. 

II.   EFFECT  OF  CEREBRAL  STATES  (EMOTIONAL  STATES, 
INTELLECTUAL  PROCESSES) 

In  the  dog  the  cerebral  processes  of  joy,  fear,  anger,  eagerness 
(for  food),  attention,  etc.,  cause  temporary  inhibition  of  the  gastric 
hunger  contractions.  This  inhibition  takes  place  by  way  of  the 
splanchnic  nerves,  not  by  a  depression  of  the  vagus  tonus.  This, 
again,  points  to  an  unusual  independence  of  the  vagogastric  tonus 
apparatus.  The  sight  or  smell  of  food  on  the  part  of  the  starving 
dog  does  not  initiate  or  augment  the  gastric  hunger  contractions. 
Dr.  Luckhardt  has  recently  shown  that  when  the  sleeping  dog 
dreams  the  gastric  hunger  contractions  are  inhibited  in  the  same 
way  that  cerebral  and  emotional  processes  tend  to  inhibition  of 
the  coQtraction  when  the  animal  is  awake. 

In  man  intellectual  processes  (attention,  reading,  figuring, 
arguing)  have  no  distinct  influence  on  the  course  of  the  hunger 
period.  Actual  anxiety  causes  temporary  inhibition  (probably 
through  the  splanchnics) .  We  have  not  been  in  a  position  to  make 
observations  on  the  effect  of  actual  anger,  fear,  and  joy,  but  there 
is  no  reason  to  believe  that  these  processes  act  differently  in  man 
from  that  in  the  dog.  In  man  we  have  paid  particular  attention 
to  the  effects  of  seeing  and  smelling  palatable  food,  as  it  seemed  a 
priori  reasonable  that  the  impulses  generated  by  these  stimuli 


152        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

might  make  more  intimate  connection  with  the  vagogastric  tonus 
apparatus.  Cannon  assumes  a  ^'pyschic  gastric  tonus"  analogous 
to  the  ^'psychic  secretion"  of  gastric  juice.  Glucksmann  states 
that  the  borborygmi  are  increased  in  rate  and  intensity  on  seeing 
and  smelling  palatable  food.  He  ascribes  this  to  increased  gastric 
contraction.  Extensive  experiments  on  Mr.  V.  and  on  the  author 
seem  to  show  that  this  is  not  the  case.  These  stimuli  neither  initiate 
nor  augment  the  gastric  tonus  and  hunger  contractions;  so  far  as 
they  influence  them  at  all,  it  is  in  the  direction  of  inhibition.  One 
of  the  tests  on  the  author  might  be  given.  Before  beginning  the 
five  days'  starvation  period,  our  colleague,  Dr.  Luckhardt,  was 
asked  to  bring  in,  unknown  to  the  author,  a  tray  of  choice  food  in 
the  midst  of  a  hunger  period.  The  arrangements  being  made  the 
matter  was  dismissed  from  the  author's  thoughts.  At  one  o'clock 
on  the  morning  of  the  fourth  starvation  day  the  subject  was  asleep 
and  the  record  showed  him  to  be  in  the  midst  of  a  period  of  vigorous 
and  regular  hunger  contractions.  He  was  awakened  to  behold 
Dr.  Luckhardt  and  the  assistant  enjoying  a  feast  of  porterhouse 
steak  with  onions,  fried  potatoes,  and  a  tomato  salad.  The  tray 
of  edibles  was  placed  not  more  than  4  inches  from  the  subject's 
face,  and  the  delicious  odor  of  the  food  filled  his  nostrils.  He  felt 
the  hunger  pangs  as  unusually  intense,  and  there  was  considerable 
salivation.  However,  the  gastric  hunger  contractions  were  not 
increased  either  in  rate  or  intensity.  In  a  few  minutes,  on  the 
contrary,  the  hunger  contractions  became  weaker  and  the  intervals 
between  them  greater,  and  the  period  terminated  by  this  gradual 
depression  much  sooner  than  it  probably  would  have  done  in  the 
absence  of  the  dinner  scene.  This  was  undoubtedly  due  to  local 
acid  inhibition  from  copious  secretion  of  appetite  gastric  juice. 

When  the  hungry  individual  sees  or  smells  good  food  the  gastric 
hunger  pangs  are  more  intense,  although  there  is  no  change  or  even 
when  there  is  some  decrease  in  the  strength  of  the  gastric  hunger 
contractions.  This  is  therefore  a  phenomenon  of  central  rein- 
forcement. 

Our  data  on  normal  men  and  dogs  seem  incapable  of  any  other 
interpretation  than  that  the  vagogastric  tonus  apparatus,  so  far 


NERVOUS  CONTROL  OF  THE  HUNGER  MECHANISM      153 

as  it  concerns  the  empty  stomach,  occupies  a  unique  and  physiologi- 
cally isolated  position  in  the  way  of  nervous  control,  while  the 
inhibitory  apparatus  via  the  splanchnic  nerves  is  readily  influenced 
by  central  and  reflex  processes.  We  feel,  however,  that  these 
observations  must  be  extended  to  other  groups  of  vertebrates  as  well 
as  to  such  pathological  cases  in  man  in  which  there  are  indications 
of  abnormalities  of  the  vagogastric  tonus  before  final  explanations 
are  attempted  or  speculation  indulged  in  as  to  the  usefulness  of  this 
physiological  isolation. 

This  evidence  for  the  physiological  isolation  of  the  hunger 
mechanism  in  the  way  of  positive  cerebral  or  central  control  is  of 
interest  in  connection  with  the  view  that  the  cravings  of  hunger 
and  appetite  are  subjective  and  largely  a  matter  of  habit,  and  that 
the  periodicity  or  intensity  of  these  cravings  may  be  altered  almost 
at  the  will  of  the  individual.    Chittenden  states  this  view  as  follows  : 

The  so-called  cravings  of  appetite  are  largely  artificial  and  mainly  the 
result  of  habit.  Anyone  with  a  little  persistence  can  change  his  or  her  habits 
of  life,  change  the  whole  order  of  cravings,  thereby  indicating  that  the  latter 
are  essentially  artificial  and  have  no  necessary  connection  with  the  welfare  or 
needs  of  the  body.  The  man  who  for  some  reason  deems  it  advisable  to  adopt 
two  meals  a  day  in  place  of  three  or  four  at  first  experiences  a  certain  amount 
of  discomfort,  but  eventually  the  new  habit  becomes  a  part  of  the  daily  routine, 
and  the  man's  life  moves  forward  as  before,  with  perfect  comfort  and  without  a 
suggestion  of  craving  or  a  pang  of  hunger. 

Our  studies  of  the  hunger  mechanism  seem  to  show  that  the 
foregoing  view  is  essentially  wrong.  •  In  the  normal  individual 
the  gastric  hunger  periods  begin  as  soon  as  the  stomach  is  empty 
and  continue  (in  the  absence  of  inhibitory  processes)  as  long  as 
the  stomach  is  empty,  irrespective  of  the  time  of  day  or  night,  and 
without  reference  to  the  time  the  individual  is  accustomed  to  eat. 
In  individuals  accustomed  to  the  usual  three  meals  in  daytime  and 
to  sleep  during  the  night  the  gastric  hunger  periods  are  more 
frequent  and  usually  more  vigorous  during  the  night  (in  sleep) 
than  during  the  day,  provided,  of  course,  the  stomach  is  empty. 
In  the  normal  individual  the  empty  stomach  exhibits  periodic 
hunger  activity,  and  there  is  no  evidence  to  show  that  this  primary 
automatism  of  the  empty  stomach  is  in  the  least  influenced  by 


154        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

eating  one  or  by  eating  five  meals  a  day.  The  basis  for  the  view 
that  the  time  of  appearance  of  the  ''cravings  of  hunger"  can  be 
changed  at  will  is  probably  to  be  sought  in  the  fact  that  the  milder 
hunger  contractions  do  not  enter  consciousness  as  pangs  of  hunger  if 
the  individual's  attention  is  directed  into  other  channels.  They  are 
felt  as  hunger  pangs  if  the  individual's  attention  is  directed  toward 
food  and  eating.  The  attention  is  thus  directed,  consciously  or 
subconsciously,  about  the  time  the  individual  is  accustomed  to  eat. 
The  periodicity  of  this  subjective  attention  to  the  milder  hunger 
cravings  can  probably  be  altered  by  training.  But  this  applies 
only  to  relatively  mild  pangs  of  hunger.  The  more  severe  "  cravings 
of  hunger"  caused  by  the  gastric  hunger  tetanus  rise  above  the 
limen  of  consciousness,  except  in  deep  sleep  or  under  conditions 
of  cerebral  process  involving  intense  interest.  When  an  individual 
who  is  accustomed  to  eat  three  times  a  day  turns  to  a  regimen  of 
one  meal  a  day,  the  quantity  of  food  ingested  in  that  one  meal  is 
much  greater  than  that  at  any  one  of  the  three  meals  a  day  regi- 
men. The  emptying  of  the  stomach  and  the  appearance  of  the 
pangs  of  hunger  are  correspondingly  delayed.  The  view  that 
prompt  appearance  and  the  persistence  of  the  gastric  hunger 
activity  in  the  empty  stomach  have  no  relation  to  the  actual  need 
of  the  individual  for  food  cannot  be  seriously  maintained  for  the 
normal  animal. 

III.      INFLUENCE    OF   THE   LOWER  BRAIN  CENTERS    (mID-BRAIN 
medulla)    on  the   gastric  hunger  CONTRACTIONS 

The  most  direct  and  at  the  same  time  the  least  objectionable 
method  of  attack  on  this  problem  is  the  section  of  the  extrinsic 
nerves  to  the  stomach,  although  this  operation  abolishes  not  only 
all  direct  influences  from  the  brain  of  a  motor  or  inhibitory  type, 
but  also  the  central  reflexes  (motor  or  inhibitory)  that  may  be 
called  into  action  through  the  sensory  nerves  in  the  stomach.  The 
splanchnic  nerves  were  sectioned  through  a  median  incision. 
The  vagi  nerves  were  sectioned  2  to  3  cm.  above  the  diaphragm, 
thus  leaving  the  fibers  to  the  esophagus,  the  heart,  and  the  lungs 
intact. 


NERVOUS  CONTROL  OF  THE  HUNGER  MECHANISM      155 

I.  Complete  section  of  the  splanchnic  nerves. — Observations  were 
made  on  five  dogs  with  complete  sections  of  the  splanchnic  nerves 
on  both  sides.  The  longest  period  of  observation  after  the  splanch- 
nic section  was  two  months.  Observations  were  in  some  cases 
begun  two  hours  after  the  operation.  When  the  records  of  these 
five  dogs  are  viewed  as  a  whole,  it  is  clear  the  complete  section 
of  the  splanchnic  nerves  in  dogs  increases  the  gastric  tonus  and  aug- 
ments the  gastric  hunger  contractions.  The  hunger  contractions 
become  more  rapid  and  continuous,  that  is,  there  is  less  evidence 
of  the  periodic  groups  with  intervening  periods  of  relative  quies- 
cence. It  is  not  uncommon  to  observe  contractions  at  the  rate  of 
about  two  per  minute  during  an  entire  observation  period  of  2  to  4 
hours.  The  section  of  the  splanchnic  nerves  does  not  aboHsh  the 
periodicity  completely,  however.  It  seems  to  be  a  question  of 
relative  degree  of  gastric  tonus.  If  for  any  reason  the  tonus  of 
the  empty  stomach  is  relatively  low  on  any  day,  the  hunger  con- 
tractions are  less  frequent,  and  there  is  greater  evidence  of  periods 
of  relative  quiescence.  We  desire  to  emphasize  the  fact  that  this 
conclusion  is  based  on  the  observations  as  a  whole.  Even  the  dogs 
with  the  splanchnic  nerves  sectioned  showed  on  some  days  no 
greater  tonus  of  the  empty  stomach  and  no  greater  rate  and  per- 
sistence of  the  gastric  hunger  contractions  than  does  the  dog  with 
these  nerves  intact.  And  occasionally  a  dog  with  the  splanchnic 
nerves  intact  exhibits  as  great  a  degree  of  gastric  tonus  and  rate 
and  persistence  of  the  gastric  hunger  contractions  as  the  maximum 
observed  in  dogs  with  the  splanchnic  nerves  cut.  This  is  to  be 
expected,  as  by  section  of  these  nerves  one  eliminates  only  one 
(and  in  the  normal  animal  probably  one  of  the  least  important)  of 
the  factors  in  the  motor  activity  of  the  empty  stomach.  The 
conditions  that  affect  the  stomach  through  the  blood  and  through 
the  vagi  are  still  subject  to  practically  the  same  variations  as  in  the 
animal  with  the  splanchnic  nerves  intact. 

After  complete  section  of  the  splanchnic  nerves  the  psychic  or 
reflex  inhibition  of  the  gastric  hunger  contractions  is  greatly  dimin- 
ished. The  stimuli  that  cause  anger,  fear,  pain,  joy,  or  pleasure 
no  longer  lead  to  complete  cessation  of  the  hunger  contractions. 


156        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

The  maximum  effect  is  a  slight  and  transitory  weakening  of  the 
contractions.  It  is  therefore  evident  that  the  inhibitory  fibers  in 
the  splanchnic  nerves  (and  possibly  also  the  secretory  fibers  of  the 
adrenals)  constitute  the  main  efferent  path  in  this  type  of  inhibition. 
The  slight  degree  of  inhibition  usually  in  evidence  after  section 
of  the  splanchnic  nerves  must  be  due  to  some  central  inhibition  of 
the  vagus  tonus  or  to  action  of  the  few  inhibitory  fibers  in  the  vagi. 

Particular  attention  was  given  to  the  effect  of  seeing  and 
smelling  food  on  the  hunger  contractions  in  these  dogs  with  section 
of  the  splanchnic  nerves,  in  order  to  determine  whether  these 
stimuli  augment  the  tonus  of  the  vagi  and  thus  increase  the  hunger 
contractions.  The  results  were  negative.  Even  with  the  greater 
part  of  the  extrinsic  inhibitory  fibers  to  the  stomach  eliminated,  the 
sight,  smell,  and  taste  of  food  not  only  fail  to  inhibit  or  augment 
the  gastric  hunger  contractions,  but,  so  far  as  these  stimuli  affect 
the  stomach  at  all,  it  is  in  the  direction  of  inhibition  of  the  hunger 
movements.  The  appareut  increase  in  the  intensity  of  the  hunger 
pangs  in  man  on  seeing  or  smelling  palatable  food  must  therefore 
be  essentially  a  central  phenomenon  of  "  f acihtation  "  or  Bahnung. 

2.  The  section  of  the  vagi. — Section  of  both  vagi  in  the  chest  was 
made  in  three  dogs,  and  after  this  operation  observations  on  the 
gastric  hunger  contractions  were  continued  for  from  two  weeks  to 
three  months.  Observations  were  made  in  some  cases  two  hours 
after  the  vagi  section. 

Section  of  the  vagi  leaves  the  empty  stomach  on  the  whole  per- 
manently hypotonic;  that  is,  at  least  for  a  period  of  up  to  three 
months  after  the  operation.  The  tonus  of  the  empty  stomach  in 
these  dogs  varies  somewhat  from  day  to  day,  and  occasionally  the 
tonus  may  approach  that  of  a  dog  with  the  vagi  intact,  but  on 
the  whole  the  tonus  is  permanently  much  lower  than  normal. 
This  is  evident,  not  only  from  the  observations  by  means  of  the 
balloon  in  the  gastric  cavity,  but  also  on  direct  inspection  and  by 
palpation  (introducing  the  finger  through  the  fistula). 

The  hunger  contractions  of  the  empty  stomach  are  changed 
mainly  in  rate  and  regularity.  The  duration  of  each  individual 
contraction  is  about  normal,  or  on  the  whole  less  than  normal. 


NERVOUS  CONTROL  OF  THE  HUNGER  MECHANISM      157 

The  long-drawn-out  contractions  or  tetanus  are  rarely  seen.  But 
the  intervals  between  the  contractions  vary  on  the  whole  from 
2  to  5  nlinutes  or  even  up  to  8  minutes.  The  strength,  or  rather 
the  amplitude,  of  the  individual  contractions  may  appear  greater 
than  normal,  evidently  because  the  contractions  start  rather  sud- 
denly and  without  any  marked  preliminary  increase  in  tonus,  and 
the  maximal  contractions  are  evidently  so  complete  that  all  the  air 
is  forced  out  of  the  balloon.  These  contractions  may  continue  of 
fairly  uniform  amplitude  and  rate  for  2  to  3  hours,  that  is,  during 
a  whole  observation  period.  The  contractions  vary  in  strength 
and  rate  from  day  to  day,  and  on  some  days  they  may  be  completely 
absent  during  the  entire  observation  period  (2  to  4  hours). 

The  periodicity  of  the  hunger  rhythm  is,  on  the  whole,  obscured, 
except  on  the  days  when  the  gastric  tonus  approached  that  in 
normal  dogs.  On  such  days  the  contractions  appear  at  shorter 
intervals,  and  tend  to  fall  into  groups  similar  to  those  in  normal 
dogs.  Periods  of  gastric  hunger  contractions  of  normal  rate  and 
intensity  have  been  observed  as  early  as  12  hours  after  complete 
section  of  the  vagi  in  the  chest.  The  period  of  most  powerful 
hunger  contractions  so  far  observed  in  any  dog  was  recorded  in  one 
dog  24  hours  after  the  vagi  section.  The  dog  had  during  the  four 
weeks  preceding  the  vagi  section  showed  almost  invariably  the 
type  II  rhythm.  It  was  therefore  a  dog  with  unusually  intense 
gastric  motor  activity.  The  complete  section  of  the  vagi  causes 
on  the  whole  less  depression  in  dogs  that  exhibit  great  hunger 
contractions  while  the  vagi  are  intact.  The  variations  in  the  rate 
and  intensity  of  the  gastric  hunger  contractions  in  different  dogs 
are  therefore  primarily  due  to  individual  variations  in  the  condition 
of  the  stomach  rather  than  to  variations  in  the  central  innervation 
or  the  central  inhibition. 

In  the  dogs  with  the  vagi  sectioned,  but  the  splanchnic  nerves 
intact,  the  ^'psychic"  or  reflex  inhibition  of  the  gastric  hunger 
contractions  is  still  in  evidence,  but  the  inhibition  appears  not  to 
be  so  marked  as  when  the  vagi  are  intact.  Accurate  comparisons 
are,  however,  difficult  to  make  because  of  the  lowered  tonus  and 
the  usual  long  intervals  between  the  hunger  contractions  after 


158        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

section  of  the  vagi.  We  expected  an  augmentation  of  the  inhibition 
through  the  splanchnics  after  the  vagi  section.  Instead  of  finding 
this  to  be  the  case;  there  actually  appeared  a  gradual  diminution 
in  the  influence  of  the  splanchnic  nerves  on  the  empty  stomach  in 
the  dog  observed  for  3  months  after  section  of  the  vagi.  It  was 
not  due  to  the  regeneration  of  the  vagi  fibers,  and  consequent 
restoration  of  the  vagus  tonus.  If  further  work  should  establish 
this  as  a  fact,  we  should  have  a  significant  instance  of  physiological 
readjustment — either  an  actual  diminution  in  the  inhibitory  im- 
pulses through  the  splanchnics  in  consequence  of  a  dynamic 
readjustment  in  the  central  nervous  system,  or  else  an  increased 
resistance  ("tolerance")  to  the  splanchnic  impulses  on  the  part  of 
gastric  motor  mechanism.  It  is  also  evident  from  this  experiment 
that  if  adrenalin  is  a  factor  in  the  inhibition  of  the  gastric  contrac- 
tions via  the  splanchnic  nerves,  section  of  the  visceral  branches  of 
the  vagi  leads  to  a  decreased  output  of  this  substance  from  the 
adrenal  gland  under  the  influence  of  the  splanchnic  nerves. 

3.  Section  of  both  splanchnic  and  both  vagi  nerves. — Complete 
sections  of  the  splanchnic  and  vagi  nerves  were  made  on  four  dogs 
and  observations  made  on  the  gastric  hunger  contractions  for  30  to 
60  days  after  the  operation.  The  sections  of  the  splanchnic  nerves 
were  made  7  days  after  the  section  of  the  vagi.  After  this  complete 
isolation  of  the  dog's  stomach  from  the  central  nervous  system, 
there  is  practically  a  permanent  hypotonus  of  the  stomach  except 
under  conditions  of  prolonged  starvation.  The  gastric  hunger 
contractions  are  much  the  same  as  when  the  vagi  alone  are  severed. 
The  contractions  are  usually  of  great  amplitude,  but  the  intervals 
between  the  contractions  are  frequently  longer  than  in  normal  dogs. 
The  grouping  of  the  contractions  in  periods  is  usually  in  evidence. 
These  contractions  of  the  isolated  and  empty  stomach  were  present 
10  to  20  hours  after  the  vagi  section,  and  there  was  some  improve- 
ment in  the  rhythm  or  an  approach  toward  the  normal  tonus  and 
contraction  rate  during  the  30  to  60  days  of  observation.  On  the 
whole,  the  hunger  contractions  of  the  isolated  stomach  conform 
to  type  I.  The  type  II  is  rare  except  during  prolonged  starvation. 
Short  periods  (2  to  3  minutes)  of  incomplete  tetanus  are  frequently 


NERVOUS  CONTROL  OF  THE  HUNGER  MECHANISM      159 

seen,  especially  during  prolonged  starvation,  and  during  the  first 
half  of  the  hunger  period.  It  is  therefore  clear  that  all  the  essential 
characteristics  of  the  hunger  contractions  of  the  empty  stomach 
are  determined  by  the  local  gastric  mechanisms  rather  than  by  the 
character  of  the  central  innervation  or  the  central  inhibition. 

Cannon  has  reported  observations  on  the  effects  of  vagi  and 
splanchnic  section  on  the  gastric  movements  of  digestion  in  cats. 
Section  of  the  splanchnic  nerves  did  not  affect  the  movements  of 
digestion;  section  of  the  vagi  caused  slowing  and  weakening  of 
the  peristalsis  of  digestion,  but  the  normal  rate  of  peristalsis  was 
practically  restored  in  a  few  days.  Combined  vagi  and  splanchnic 
section  left  the  digestive  movements  of  the  stomach  practically 
normal,  even  shortly  after  the  operation.  It  seems  that  section  of 
the  vagi  or  complete  section  of  the  vagi  and  the  splanchnic  nerves 
in  dogs  causes  on  the  whole  a  greater  change  in  the  movements  of 
the  empty  stomach  than  does  the  same  lesion  in  cats  in  case  of  the 
movements  of  the  filled  stomach.  This  probably  means  that  the 
tonus  of  the  vagi  plays  a  greater  role  in  the  movements  of  the 
empty  than  in  the  movements  of  the  filled  stomach.  For  it  is  not 
likely  that  there  is  such  marked  difference  in  the  relative  importance 
of  the  vagi  nerves  in  cats  and  dogs. 

The  changes  in  the  character  of  the  gastric  hunger  contractions 
after  isolation  of  the  stomach  from  the  central  nervous  system 
seem  primarily  due  to  the  persistent  hypotonus.  This  is  indicated 
by  the  fact  that  on  days  when  the  stomach  of  a  normal  dog  shows 
relatively  sHght  tonus  the  hunger  contractions  approach  the  type 
shown  by  the  isolated  stomach,  and  on  days  when  the  isolated 
stomach  exhibits  tonus  approaching  that  in  normal  dogs  the  hunger 
contractions  tend  to  assume  the  normal  type.  Occasionally  records 
are  obtained  from  the  empty  and  isolated  stomach  that  practically 
demonstrate  the  above  point.  During  a  period  of  relatively  slow 
hunger  rhythm  the  tonus  for  some  unknown  reason  may  increase 
markedly  for  periods  of  varying  length,  and  during  these  periods 
the  hunger  contractions  are  identical  in  rate  and  character  with 
those  of  the  intact  stomach  in  normal  (strong)  tonus.  In  one  of 
the  dogs  with  the  vagi  and  splanchnic  nerves  sectioned  six  days 


i6o        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

of  fasting  led  to  the  appearance  of  periods  of  very  great  gastric 
tonus,  and  during  these  periods  (virtually  periods  of  incomplete 
tetanus)  the  gastric  contractions  assumed  the  form  of  type  III. 

However,  the  details  of  the  changes  in  the  hunger  rhythm 
after  isolation  of  the  stomach  from  the  central  nervous  system 
seem  of  minor  importance  in  this  connection.  The  essential  point 
is  that  since  the  empty  stomach,  completely  isolated  from  the 
central  nervous  system,  does  exhibit  the  typical  hunger  contrac- 
tions, the  primary  role  of  the  gastric  nerves  is  that  of  modifying 
or  regulating  essentially  automatic  mechanisms  in  the  stomach  wall. 
In  other  words,  the  extrinsic  nerves  to  the  stomach  play  a  role 
similar  to  that  of  the  nerves  to  the  heart  in  the  regulation  of  the 
heart  rhythm.  Further  analysis  of  the  hunger  mechanism  must 
be  directed  primarily  to  the  intrinsic  neuromuscular  apparatus  of 
the  stomach,  and  secondarily  to  the  factors  that  control  the  vagus 
tonus. 


CHAPTER  XI 

THE  NERVOUS  CONTROL  OF  THE  HUNGER  MECHANISM 

{Continued) 

I.      INHIBITION  FROM  THE  MOUTH  IN  MAN  AND  OTHER  ANIMALS 

Our  gastric  fistula  man,  Mr.  V.,  offers  an  exceptional  oppor- 
tunity for  studying  the  relations  of  certain  conscious  states,  par- 
ticularly those  associated  with  foods  and  with  eating,  on  the 
activities  of  the  empty  stomach.  The  esophagus  is  completely 
closed  at  the  level  of  the  upper  end  of  the  sternum,  so  that  nothing 
can  enter  the  stomach  from  the  mouth.  The  swallowing  mechan- 
isms are  normal,  and  the  man  can  swallow  and  hold  in  the  eso- 
phageal pouch  about  25  c.c.  of  material.  The  gustatory  (and 
olfactory)  sense  is  normal.  The  senses  of  thirst  and  hunger  are 
normal.  He  masticates  his  food  in  the  usual  way,  and  the  chewing 
processes  are  accompanied  by  the  normal  conscious  states.  The 
masticated  food  is  placed  in  a  syringe  and  introduced  into  the 
stomach  through  the  fistula,  which  does  not  involve  any  pain  or 
discomfort,  and  the  man  is  adjusted  to  this  condition,  as  this  has 
been  his  method  of  feeding  for  the  last  twenty  years.  Because  of 
the  ample  size  of  the  gastric  fistula  the  man  may  sit  down  at  the 
dinner  table,  see,  smell,  taste,  and  chew  his  food  in  the  usual  man- 
ner up  to  the  point  of  introducing  the  food  through  the  fistula, 
while  tracings  are  being  taken  of  a  tonus  and  the  movements  of 
the  stomach,  and  records  made  of  the  secretion  of  the  gastric  juice. 

We  know,  particularly  through  the  researches  of  Pavlov  on 
dogs,  and  from  many  observations  on  man,  that  when  appetite  is 
present  the  sight,  smell,  taste  (especially  taste)  of  palatable  foods 
causes  a  reflex  secretion  of  gastric  juice,  the  so-called  "psychic 
secretion."  The  efferent  nerve- fibers  for  this  reflex  reach  the 
stomach  through  the  vagi.  The  more  recent  work  of  Cannon  and 
others  has  demonstrated  that  the  tonus  of  the  stomach  musculature 
is  also  primarily  dependent  on  efferent  nervous  impulses  through 

161 


1 62        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

the  vagi.  A  certain  degree  of  tonus  is  normally  a  prerequisite  for 
peristalsis  or  contractions  in  the  empty  stomach.  The  suggestion 
is  therefore  obvious  that  the  same  stimuli  which  lead  to  psychic 
secretion  of  gastric  juice  may  at  the  same  time  cause  an  augmenta- 
tion of  the  tonus  and  the  contractions  of  the  stomach  musculature. 
Cannon  postulated  such  a  "psychic  tonus,"  but  no  evidence  for 
its  existence  has  been  recorded. 

It  is  a  universal  experience  of  normal  persons  that  the  sight  or 
smell  (or  even  the  memory)  of  palatable  foods  seems  to  induce 
hunger  and  appetite,  or  intensify  these  sensations  if  they  are  already 
present.  The  simplest  explanation  of  this  fact  would  be  that  the 
smell  or  taste  of  palatable  foods  initiates  or  augments  the  stomach 
contractions,  thus  increasing  the  hunger  sensation  by  increasing  the 
intensity  of  the  gastric  stimulation.  The  facts,  at  least  in  man  and 
dogs,  are  the  very  opposite  of  those  demanded  by  this  hypothesis. 

There  are  two  sources  of  error  in  experiments  of  this  character. 
In  the  first  place,  the  periods  of  contraction  of  the  empty  stomach 
vary  in  intensity  and  duration,  and  the  intervening  periods  of 
relative  quiescence  vary  in  length.  The  periods  of  quiescence  may 
be  interrupted  by  occasional  contractions.  This  being  the  case, 
the  initiation  of  stomach  contractions  simultaneously  with  tasting 
palatable  food  during  quiescence  of  the  stomach,  for  example,  may 
be^  a  mere  coincidence.  An  augmentation  of  the  contractions 
seemingly  due  to  tasting  food  during  a  contraction  period  may 
simply  be  the  usual  increase  in  strength  of  the  stomach  contraction 
during  such  period.  In  the  same  way,  if  tasting  food  toward  the 
end  of  a  contraction  period  should  be  followed  by  cessation  of 
the  stomach  contractions,  this  apparent  inhibition  may  be  a  coin- 
cidence, the  cessation  of  the  contractions  being  ''spontaneous" 
and  not  casually  connected  with  the  tasting  of  food.  These  diffi- 
culties were  realized  before  the  work  was  undertaken,  as  it  was 
preceded  by  an  extended  survey  of  the  ''spontaneous"  stomach 
movements  when  not  interfered  with  experimentally.  Because  of 
the  variabiHty  of  the  "spontaneous"  stomach  activity,  the  indi- 
vidual test  must  be  repeated  a  great  number  of  times,  and  little 
or  no  significance  can  be  ascribed  to  exceptional  results. 


NERVOUS  CONTROL  OF  THE  HUNGER  MECHANISM       163 

A  source  of  error,  more  serious  because  not  so  readily  controlled, 
lies  in  certain  subjective  states  of  an  inhibitory  character.  Pavlov 
found  that  while  the  sight  and  smell  (yi  palatable  foods  ordinarily 
caused  "psychic"  secretion  of  gastric  juice  in  dogs  when  hungry, 
if  the  dogs  knew  from  past  experience  that  they  were  not  to  be 
permitted  to  eat  the  food,  the  same  stimuli  caused  no  secretion. 
We  may  have  analogous  conditions  in  regard  to  the  stomach  tonus 
and  movements.  It  is  possible  that,  no  matter  how  great  the 
hunger  or  appetite  in  man,  the  knowledge  that  the  seeing,  smelling, 
or  tasting  food  was  part  of  an  experiment  might  initiate  cerebral 
processes  of  an  inhibitory  character.  This  source  of  error  has  been 
controlled  in  two  ways:  (i)  in  Mr.  V.'s  case  the  mastication  or 
tasting  food  was  made  part  of  his  ordinary  routine  in  preparing 
the  food  to  be  put  into  the  stomach,  and  the  man  knew  that  as 
soon  as  the  food  was  prepared  it  would  be  introduced  into  the 
stomach  in  the  usual  way;  (2)  records  were  made  of  the  presence 
or  absence  of  the  psychic  secretion  of  gastric  juice.  If  the  tasting 
and  chewing  of  food  start  a  copious  flow  of  gastric  juice,  we  can 
infer  that  the  tasting  and  chewing  do  not  give  rise  to  cerebral 
processes  of  an  inhibitory  character. 

I.  Inhibition  of  the  hunger  contractions  of  the  empty  stomach  by 
stimulation  of  the  gustatory  end  organs  in  the  mouth. — -The  substances 
used  for  stimulation  were  sugar  (solid  and  in  solution),  quinine  in 
weak  solution,  sodium  chloride  (solid  and  in  solution),  weak  solu- 
tions of  acetic  and  hydrochloric  acids.  Tests  were  made  at  all 
stages  of  activity  of  the  empty  stomach.  The  results  were  uniform 
and  practically  identical  for  the  four  kinds  of  stimuli  employed. 
If  the  substances  were  used  in  sufficient  concentrations  to  affect 
the  stomach  activity,  the  effects  were  inhibition  of  the  tonus  and 
contractions.  These  inhibitory  effects  follow  promptly  on  placing 
the  substances  in  the  mouth,  and  disappear,  on  the  whole,  very 
soon  after  removing  the  substances  from  the  mouth  and  rinsing 
the  mouth  with  warm  water.  Quinine  and  the  acid  produced  the 
longest  inhibitory  after-effects,  probably  because  of  the  difficulty 
in  completely  removing  these  substances  by  rinsing  the  mouth 
with  water. 


1 64        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

This  gustatory  inhibition  is,  on  the  whole,  proportional  to  the 
strength  of  the  stimuli  (i.e.,  the  concentration  of  the  substance) 
and  varies  inversely  with  the  degree  of  the  stomach  activity.  Thus 
a  weak  solution  of  acetic  acid  that  produced  distinct  inhibition 
during  the  first  stage  of  a  period  of  hunger  contraction  when  the 
individual  contractions  are  relatively  weak  may  have  little  or  no 
effect  when  placed  in  the  mouth  during  the  tetanus  stage  of  the 
contractions. 

If  the  gustatory  stimuli  are  weak  and  allowed  to  act  in  the 
mouth  for  5  to  15  minutes,  the  stomach  ^'escapes"  from  the  inhibi- 
tion gradually.  This  is  practically  true  of  sweet  (sugar).  Moder- 
ate strength  of  acids  and  quinine  may  hold  the  stomach  in  nearly 
complete  inhibition  up  to  15  minutes.  The  stimulating  substances 
are,  of  course,  gradually  diluted  by  the  secretion  of  saliva. 

Are  these  gustatory  inhibitions  primary  and  relatively  simple 
reflexes  independent  of  the  states  of  consciousness,  or  are  they  of 
the  type  of  conditional  reflexes,  and  therefore  due  to  cerebral  states 
of  unpleasant  affective  tone  ?  This  question  must  be  answered  by 
experiments  on  lower  animals  with  less  development  of  the  cere- 
brum and  especially  on  decerebrated  mammals  and  on  so-called 
''acephalic"  infants. 

2.  Inhibition  of  the  tonus  and  the  contractions  of  the  empty  stomach 
by  chewing  indiferent  substances. — ^We  have  been  unable  to  obtain 
any  definite  evidence  of  inhibition  of  the  stomach  movements  by 
the  movements  of  mastication  when  the  mouth  is  empty.  But 
chewing  what  may  be  called  indifferent  substances,  such  as  paraffin, 
gum,  or  straw,  produces  distinct  inhibition.  Most  of  the  experi- 
ments were  made  by  chewing  paraffin.  Most  people  can  chew 
paraffin  without  any  sensation  of  a  disagreeable  or  unpleasant  tone, 
or  of  a  pleasant  tone,  either,  for  that  matter.  Mr.  V.  said  he  *'did 
not  care  for  the  paraffin,"  naturally.  But  he  has  no  dislike  for  it. 
The  chewing  of,  indifferent  substances  produces,  on  the  whole,  less 
inhibition  than  do  gustatory  stimuH.  The  stomach  "escapes" 
from  the  inhibition  in  a  few  minutes,  even  though  the  chewing  is 
continued  with  uniform  vigor.  The  chewing  usually  fails  to  pro- 
duce any  effects  in  the  tetanus  stage  of  the  stomach  activity. 


NERVOUS  CONTROL  OF  THE  HUNGER  MECHANISM      165 

Inasmuch  as  the  masticatory  movements  do  not  cause  inhibition 
if  the  mouth  is  empty,  we  may  conclude  that  inhibition  produced 
by  chewing  indifferent  substances  is  initiated  by  mechanical 
stimulation  of  afferent  nerve-endings  in  the  mouth. 

3.  Inhibition  of  the  tonus  and  the  hunger  contractions  of  the  empty 
stomach  by  chewing  palatable  foods  when  hunger  and  appetite  are 
present. — Tests  were  made  with  all  food  substances  palatable  to 
Mr.  V.  and  during  all  stages  of  gastric  tonus  and  contractions, 
which  imply  all  degrees  of  hunger  and  appetite.  But  most  of  the 
experiments  were  made  with  meats  in  the  form  of  stews,  fricassees, 
or  pot  roasts,  fried  eggs,  and  crackers  or  bread  soaked  in  milk, 
soups,  or  meat  gravy.  The  results  are  uniform  without  exception. 
Chewing  or  tasting  palatable  foods  inhibits  the  tonus  and  the  move- 
ments of  the  empty  stomach.  The  inhibition  is  in  evidence  within 
a  few  seconds  after  placing  the  food  in  the  mouth,  and  may  or  may 
not  continue  for  some  time  after  removing  the  food  from  the  mouth 
and  rinsing  the  mouth  with  warm  water.  The  inhibition  is  least 
in  evidence  during  the  hunger  tetanus.  In  fact,  we  are  uncertain 
whether  the  chewing  of  palatable  foods  is  able  materially  to  affect 
the  stomach  in  hunger  tetanus.  It  is  difficult  to  determine  whether 
cessation  of  the  hunger  tetanus  that  follows — usually  not  very 
promptly — the  placing  of  palatable  food  in  the  mouth  is  a  ''spon- 
taneous" cessation,  or  due  to  inhibition  from  the  mouth.  The 
records  show,  however,  that  so  far  as  the  stimuli  in  the  mouth 
affect  the  processes  of  the  hunger  tetanus,  the  influence  is  in  the 
direction  of  inhibition. 

The  inhibition  of  the  motor  activity  of  the  stomach  by  chewing 
palatable  foods  does  not  appear  to  have  any  after-effects  in  the 
nature  of  increased  tonus  or  contractions.  Some  of  the  tracings 
do  suggest  a  motor  after-effect,  but  we  are  inclined  to  interpret 
them  in  a  different  way.  These  effects  are  obtained  only  when  the 
tests  are  made  during  the  relative  quiescence  of  the  stomach  or  at 
the  beginning  of  a  contraction  period  (''30-seconds  rhythm"). 
Moreover,  these  results  were  not  always  secured  even  during  these 
periods.  It  would  therefore  seem  that  these  apparent  augmentary 
after-effects  represent  the  ''spontaneous"  initiation  of  a  contraction 


1 66        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

period,  or  the  gradual  increase  in  the  magnitude  of  the  contrac- 
tions characteristic  of  the  periods  of  the  30-seconds  rhythm. 

4.  Factors  involved  in  the  inhibition  of  the  contractions  of  the 
empty  stomach  by  palatable  foods  in  the  mouth. — Boldyreff  has  reported 
that  the  contractions  of  the  empty  stomach  in  the  dog  cease  during 
the  periods  of  ''spontaneous"  secretion  of  gastric  juice.  We  know 
that  tasting  or  chewing  palatable  foods  leads  to  reflex  or  ''psychic" 
secretion  of  gastric  juice  in  mammals  (including  man).  May  not 
the  inhibition  described  above  be  an  indirect  one,  due  to  the 
secretion  of  gastric  juice,  rather  than  a  reflex  inhibition  of  more 
direct  character  ?  This  question  has  been  investigated  and  settled. 
A  rapid  secretion  of  gastric  juice  is  associated  with  cessation, 
partial  or  complete,  of  the  stomach  contractions  in  Mr.  V.  We 
shall  show  later  that  this  is  due,  not  to  the  processes  of  secretion, 
as  such,  but  to  acid  stimulation  of  nerve-endings  in  the  mucosa. 
When  the  chewing  or  tasting  of  palatable  foods  leads  to  copious 
secretion  of  gastric  juice,  this  gastric  juice  is  one  factor  in  the 
accompanying  inhibition  of  the  stomach  movements. 

We  know,  from  Pavlov's  work  on  dogs,  that  the  latent  period 
of  the  "psychic "  secretion  is  about  5  minutes.  The  latent  period  of 
the  "psychic"  secretion  in  man  is  shorter  (2  to  3  minutes).  The 
inhibition  of  the  stomach  tonus  and  movements  follows  within  a 
few  seconds  after  placing  the  food  in  the  mouth.  Hence  it  is  not 
an  acid  inhibition  from  the  stomach.  The  same  thing  can  be  shown 
when  the  tasting  or  chewing  of  the  food  produces  only  a  scanty 
secretion  of  gastric  juice.  The  inhibition  appears  in  the  normal 
way,  and  the  concentrations  reappear  on  removing  the  food  from 
the  mouth  despite  the  slow  secretion  of  gastric  juice. 

It  seems  that  a  certain  quantity  of  gastric  juice  must  accumulate 
in  the  stomach  or  the  free  hydrochloric  acid  in  the  stomach  must 
reach  a  certain  concentration  before  the  acid  inhibition  takes  place. 
Thus,  if  the  period  of  chewing  or  tasting  the  palatable  food  is  short 
(4  to  6  minutes),  the  stomach  contractions  may  reappear  at  the 
end  of  the  stimulation  in  the  mouth,  and  shortly  afterward  again 
be  inhibited  by  the  acid  gastric  juice.  This  inhibition  continues 
during  the  phase  of  rapid  "psychic"  secretion.    When  the  psychic 


NERVOUS  CONTROL  OF  THE  HUNGER  MECHANISM      167 

secretion  is  more  copious,  the  reflex  inhibition  from  the  mouth 
merges  into  the  acid  inhibition  from  the  stomach. 

5.  Inhibition  of  the  tonus  and  the  hunger  contractions  of  the  empty 
stomach  by  swallowing  movements. — It  has  been  shown  by  Cannon 
and  Lieb  for  the  dog  that  the  movements  of  swallowing  lead  to  a 
temporary  inhibition  of  the  tonus  of  the  stomach.  This  inhibition 
is  designated  the  ''receptive  relaxation"  of  the  stomach.  This 
inhibition  is  readily  demonstrated  in  man.  When  Mr.  V.  makes 
repeated  swallowing  movements  with  only  enough  saliva  in  the 
mouth  to  initiate  the  swallowing  reflex,  a  prompt  but  transitory 
inhibition  of  gastric  tonus  and  contractions  is  produced.  The 
reader  will  recall  that  the  swallowed  saHva  does  not  reach  the 
stomach,  but  collects  in  the  esophagus  pouch.  Complete  inhibi- 
tion of  the  stomach  contractions  was  never  secured  through  the 
swallowing  act,  and  when  the  stomach  is  in  the  condition  of  hunger 
tetanus,  or  in  very  strong  and  rapid  contractions  bordering  on 
tetanus,  the  mere  swallowing  movements  seem  to  have  no  effect 
on  the  stomach.  The  inhibition  of  the  stomach  tonus  due  to  the 
act  of  swallowing  is  most  readily  demonstrated  at  the  beginning 
of  a  period  of  hunger  contractions. 

6.  Relation  of  the  reflex  inhibition  of  the  tonus  and  the  movements 
of  the  empty  stomach  from  the  mouth  to  the  sensation  of  hunger. — The 
stimulation  of  the  gustatory  end  organs  in  the  mouth,  the  chewing 
of  indifferent  substances,  and  the  tasting  and  chewing  of  palatable 
foods  would  aboHsh  the  sensations  of  hunger  to  the  same  degree 
that  these  measures  inhibit  the  stomach  contractions.  The  inhibi- 
tion of  the  stomach  activity  and  the  cessation  of  the  hunger  pains 
run  parallel.  This  conclusion  is  based  on  experiments  on  a  number 
of  men  besides  Mr.  V. 

In  the  dog,  food  or  other  substances  in  the  mouth  cause  inhibition 
of  the  hunger  contractions  of  the  stomach.  But  since  these  manipu- 
lations disturb  the  animal  and  induce  salivation,  and  in  many  cases 
swallowing  movements,  the  precise  mechanism  of  the  inhibition 
must  remain  in  doubt  until  it  can  be  investigated  on  dogs  from  which 
the  cerebrum  has  been  removed,  since  most  of  the  dog's  cerebral 
pi'ocesses  (pleasant  or  unpleasant)  induce  the  same  inhibition. 


1 68        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

In  the  rabbit,  the  sight,  smell,  or  taste  of  food,  or  the  chewing 
(without  swallowing)  of  such  foods  as  cherries,  carrots,  apples, 
carrot  leaves  moistened  with  sugar,  acid,  or  quinine  do  not  inhibit 
the  stomach  contractions  (Rogers).  The  same  is  also  true  for  the 
guinea-pig  (Dr.  King) .  In  the  case  of  the  single  goat  so  far  studied, 
the  chewing  of  ordinary  food  (hay,  oats,  carrots)  appeared  to 
increase  rather  than  decrease  the  hunger  contractions  of  the  rumen. 

In  the  pigeons,  Rogers  encountered  the  same  difficulties  that  we 
met  in  the  dogs.  Any  disturbance  of  the  normal  pigeon  inhibits 
the  hunger  contractions  of  the  empty  crop.  And  since  it  is  not 
possible  to  put  food  or  other  substances  in  the  mouth  of  these  birds 
without  more  or  less  disturbance  by  the  handling,  we  cannot  be 
sure  that  the  resulting  inhibition  proceeds  from  stimulation  of 
nerves  in  the  mouth.  In  the  decerebrated  bird,  visual  and  auditory 
stimuli  do  not  inhibit  the  crop,  but  handling  the  bird,  as  in  feeding 
or  placing  anything  in  the  mouth,  causes  inhibition.  If  the  dis- 
turbing factors  other  than  the  mouth  stimulation  could  be  ehm- 
inated,  it  is  likely  that  the  mouth  stimulation  alone  would  cause 
little  or  no  inhibition  unless  accompanied  by  swallowing. 

In  the  frog,  stimulation  of  the  nerve-endings  in  the  mouth  by 
food  substances,  acids,  or  alkahes  cause  little  or  no  inhibition  of 
the  empty  stomach.  This  is  true  whether  the  frog  is  normal  or 
decerebrated  (Patterson) . 

It  is  thus  evident  that  the  marked  reflex  inhibition  of  the  gastric 
hunger  contractions  from  mechanical  and  chemical  stimuli  acting 
in  the  mouth  of  man  is  much  less  in  evidence,  although  not  entirely 
absent  in  the  lower  mammals,  birds,  and  frogs.  This  leads  us  to 
suspect  that  in  man  and  the  higher  animals,  where  this  reflex  is 
preponderant,  it  involves  conscious  cerebral  processes.  The  ques- 
tion could  possibly  be  settled  by  experiments  on  infants  (normal 
and  acephalic)  and  on  persons  in  very  deep  sleep. 

II.      THE   INFLUENCE   OF   STIMULATION   OF   THE    GASTRIC   MUCOSA 
ON   THE   HUNGER   CONTRACTIONS    OF   MAN 

The  character  of  the  periodic  and  continuous  motor  activity 
of  the  empty  stomach  in  man  and  other  animals  has  been  described. 
It  has  also  been  shown  that  the  contractions  of  the  empty  stomach 


NERVOUS  CONTROL  OF  THE  HUNGER  MECHANISM       169 

give  rise  to  the  sensation  of  hunger  or  the  ''hunger  pangs"  by 
stimulation  of  afferent  nerve-endings  in  the  gastric  mucosa.  We 
have  also  seen  that  in  man  the  hunger  contractions  of  the  stomach 
are  inhibited,  reflexly,  by  all  stimuli  acting  on  end  organs  of  taste 
and  general  sensations  in  the  mouth  cavity,  so  that  in  case  of 
chewing  palatable  foods  when  in  hunger  we  have  the  so-called 
psychic  secretion  of  gastric  juice  preceded  and  paralleled  by  a  psy- 
chic inhibition  of  gastric  motility  and  tonus.  It  has  also  been 
shown  that  the  hunger  contractions  persist  in  their  essential  char- 
acter after  section  of  the  nerves  connecting  the  stomach  with  the 
central  nervous  system.  If  we  are  to  attempt  to  determine  more 
specifically  the  cause  of  the  hunger  contractions  our  attention 
must  be  directed  to  the  stomach  itself.  The  contractions  of  the 
empty  stomach  may  be  due  to  any  one  of  these  four  conditions. 

I.      CONDITION   OR   STIMULATION   OF   THE   GASTRIC   MUCOSA 

The  absence  of  food  means  absence  of  mechanical  stimuli  and 
cessation  or  diminution  of  the  secretion  of  gastric  juice,  and  hence 
a  diminished  acidity.  Carbon  dioxide  may  be  secreted  into  the 
empty  stomach  and  may  act  as  the  primary  stimulus.  Carbon 
dioxide  and  other  gases  may  enter  the  stomach  from  the  intestines 
and  act  as  stimuli.  Succus  entericus,  pancreatic  juice,  and  bile 
may  enter  the  stomach  and  act  as  the  primary  stimulus  through 
alkalinity  or  by  means  of  specific  substances,  such  as  the  bile  acids. 
The  reader  will  recall  that  a  number  of  workers  maintain  that  bile 
facilitates  the  intestinal  movements. 

2.      CONDITION  OF  THE   BLOOD,    SUCH  AS   THE   RELATIVE   CONCENTRATION 
OF  NUTRIENT   SUBSTANCES,   TISSUE   METABOLITES,   AND  HORMONES 

It  is  possible  that  the  neuromuscular  apparatus  of  the  stomach 
is  specially  sensitized  to  slight  variations  in  these  substances.  While 
we  recognize  the  condition  of  the  blood  as  a  possible  factor,  it  does 
not  seem  a  probable  one;  in  the  first  place,  because  the  composition 
of  the  blood  is  on  the  whole  more  constant  thaji  the  composition  of 
the  tissues,  and  because  in  young  and  vigorous  individuals  the 
hunger  contractions  of  the  stomach  begin  as  soon  as  the  stomach 
is  empty  and  while  digestion  and  absorption  are  still  in  progress 


I70        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

in  the  intestines,  so  that  there  can  be  no  lack  of  nutrient  substances 
in  the  blood.  In  view  of  the  relative  constancy  of  the  composition  of 
the  blood  as  shown  by  all  past  work  on  the  blood  serum  and  blood 
plasma,  the  existence  of  a  periodic  fluctuation  in  the  concentration 
of  any  one  substance  in  the  blood  parallel  with  the  periodicity  of  the 
hunger  contractions  seems  improbable. 

3.   MOTOR  NERVOUS  IMPULSES  THROUGH  THE  VAGI 

It  is  well  known  that  the  tonus  of  the  stomach  depends,  in  part, 
on  impulses  from  the  vagi,  and  that  the  stimulation  of  the  peripheral 
end  of  the  vagi  induces  strong  contractions  in  the  stomach,  whether 
empty  or  filled  with  food.  It  is  also  known  that  the  stomach  is 
capable  of  carrying  out  the  movements  of  digestion  to  a  fair  degree  of 
efficiency  after  section  of  both  the  vagi  and  the  splanchnic  nerves. 
In  other  words,  the  neuromuscular  apparatus  of  the  stomach  seems 
to  be  primarily  automatic  as  regards  the  genesis  of  the  movements 
of  the  digestion. 

The  experiment  of  sectioning  the  vagi  does  not  prove  this  point, 
however.  The  experiment  does  prove  the  plasticity  of  the  gastric 
motor  mechanism.  One  would  expect  that  the  extrinsic  gastric 
nerves  bear  the  same  relation  to  the  movements  of  the  filled  and  of 
the  empty  stomach.  This  phase  of  the  problem  cannot  be  studied 
in  man.  If  it  should  develop  that  the  periodic  hunger  contractions 
of  the  empty  stomach  are  caused  by  periodic  discharges  through 
the  vagi,  the  ultimate  question  of  the  cause  of  hunger  would  again 
become  a  problem  of  physiology  of  the  central  nervous  system. 

4.      PRIMARY  AUTOMATICITY   OF  THE   LOCAL  NEUROMUSCULAR 
MECHANISM  OF  THE   STOMACH 

This  can  be  established  only  by  exclusion  of  the  three  other 
possibilities  outlined  above.  A  primarily  automatic  mechanism 
might  still  be  influenced  by  the  blood,  by  the  extrinsic  nerves,  and 
by  local  reflexes  from  the  gastric  mucosa.  The  periodicity  of  the 
automatic  activity  might  be  due,  not  to  a  parallel  periodicity  in 
any  essential  stimulus,  but  to  some  peculiarity  in  the  metabolism 
of  the  stomach  developed  as  a  special  adaptation,  similar  to  peri- 


NERVOUS  CONTROL  OF  THE  HUNGER  MECHANISM      171 

odicity  in  other  organs.  The  absence  of  the  hunger  contractions 
during  digestion,  or  possibly  the  modification  of  the  hunger  con- 
tractions into  the  movements  of  digestion,  must,  in  this  case,  be 
due  to  specific  inhibitory  or  regulatory  impulses  from  the  gastric 
mucosa. 

Mr.  V.  is  admirably  adapted  for  determining  the  relation  of 
stimulation  of  the  gastric  mucosa  to  the  hunger  movements,  as  the 
fistula  is  large  enough  to  permit  the  balloon  and  connecting  tube, 
and  a  tube  for  the  introduction  of  liquids  and  gases,  to  be  placed 
in  the  stomach  simultaneously.  The  liquids  and  gases  can  be 
introduced  with  or  without  the  man's  knowledge.  Furthermore, 
the  contents  of  the  stomach  (fluid  and  gas)  can  be  withdrawn  for 
analysis  at  any  stage  of  the  hunger  movements  and  without  any 
material  disturbance.  But  the  results  first  obtained  on  Mr.  V. 
have  been  abundantly  confirmed  on  other  individuals.  This  can 
be  done  by  simply  introducing  a  small  tube  into  the  stomach  in 
addition  to  the  balloon  with  tube  connection,  so  that  substances 
can  be  put  into  the  stomach  without  touching  the  mouth  or 
esophagus. 

I.  The  action  of  water. — Water,  at  body  temperature,  or  nearly 
ice  cold,  inhibits  the  tonus  and  the  hunger  contractions  of  the 
stomach.  The  inhibition  following  the  introduction  of  a  glass  of 
water  (100  to  200  c.c.)  directly  into  the  stomach  lasts  on  the  whole 
only  3  to  5  minutes,  and  is  never  followed  by  any  augmentation  of 
the  tonus  or  the  hunger  contractions.  The  cold  water  causes 
greater  inhibition  than  the  water  at  body  temperature.  If  the 
water  is  introduced  into  the  stomach  during  very  intense  hunger 
contractions  ("hunger  tetanus"),  there  may  be  no  perceptible 
inhibition.  In  other  words,  the  degree  of  inhibition  by  water  in 
the  stomach  is  inversely  proportional  to  the  intensity  of  the  hunger 
contractions  present  at  the  time  the  water  is  introduced.  Water, 
warm  or  cold,  introduced  directly  into  the  stomach  during  the 
period  of  relative  relaxation  and  quiescence  does  not  increase  tonus 
or  initiate  a  contraction  period. 

The  statement  that  cold  water  causes  on  the  whole  greater 
inhibition  than  water  at  body  temperature  requires  the  following 


172        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 


Fig.  1 8. — Records  of  gastric  hunger  contractions  of  Mr.  V.  A,a.txsi  teaspoonful 
of  sugar  was  put  in  the  mouth;  at  X'  the  sugar  was  rinsed  out  with  warm  water; 
showing  inhibition  of  the  stomach  contractions  by  stimulation  of  end  organs  for  the 
sense  of  sweetness.  One-half  original  size.  B,  at  X  a,  teaspoonful  of  table  salt  was 
put  in  the  mouth;  at  X'  the  salt  was  rinsed  out  with  warm  water;  showing  inhibition 
of  the  stomach  contractions.  One-half  original  size.  C,  at  X  15  c.c.  weak  acetic  acid 
was  put  in  the  mouth;  at  X'  the  mouth  was  rinsed  with  warm  water;  showing  inhibi- 
tion of  the  stomach  contractions.  One-third  original  size.  D,  X-X',  vigorous  chewing 
of  paraffin;  showing  inhibition  of  the  hunger  contractions  of  the  stomach  by  chewing 
indifferent  substances. 


NERVOUS  CONTROL  OF  THE  HUNGER  MECHANISM      173 

qualification.  The  record  of  the  stomach  movements  was  taken 
by  means  of  an  air-inflated  balloon  in  the  stomach  cavity.  Now, 
when  cold  water  is  introduced  the  water  surrounds  the  balloon,  at 
least  partly,  and  cools  the  air  in  the  balloon.  This  itself  will  lower 
the  tension  somewhat,  until  the  temperature  is  restored  to  that  of 
the  body  by  the  warming  of  the  water  or  by  the  passing  of  the 
water  into  the  intestine.    We  do  not  think  that  this  is  a  serious 


w/Uy 


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wiff*    T"''iijijlr '■ '"■"'■ 


ii'it^ 


^^r  Wj^^  U-aU^^wU^ 


Fig.  19. — A,  record  of  the  contractions  of  the  empty  stomach  of  Mr.  V.  At  X 
100  c.c.  cold  water  introduced  directly  into  the  stomach;  showing  the  temporary 
inhibition.  About  two-thirds  original  size.  B,  records  from  the  empty  stomach  of 
A.  J.  C.  At  X  introduction  of  15  c.c.  brandy  in  25  c.c.  warm  water  directly  into  the 
stomach;  showing  the  alcohol  inhibition  of  the  hunger  contractions.  C,  record  of  the 
contractions  of  the  empty  stomach  of  Mr.  V.  At  X  25  c.c.  of  human  gastric  juice 
(V.'s  own  gastric  juice,  psychic  secretion,  secured  2  hours  previously)  introduced 
into  the  stomach;  showing  the  acid  inhibition.  About  one-half  original  size.  D, 
record  from  the  empty  stomach  of  dog  with  gastric  fistula.  At  X  25  c.c.  of  0.5  per 
cent  HCl  (warm)  introduced  directly  into  stomach;  showing  the  prolonged  acid 
inhibition,  with  gradual  recovery.  Total  time  of  the  part  of  the  tracing  reproduced, 
30  minutes.     About  one-half  original  size. 


174        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

source  of  error  for  this  reason.  A  few  experiments  were  made  with 
water  at  50°  C.  This  causes  greater  inhibition  than  when  the  water 
is  at  38°  C.  Water  at  50°  C.  will,  of  course,  increase  the  air  tension 
in  the  balloon,  yet  the  inhibition  of  the  stomach  tonus  and  move- 
ments is  sufficiently  marked  to  mask  the  effect  of  slight  warming 
of  the  air. 

How  does  water  in  the  stomach  produce  this  temporary  inhibi- 
tion ?  It  goes  without  saying  that  in  these  experiments  the  water 
was  not  introduced  fast  enough  to  cause  contractions  by  distension 
of  the  stomach  wall,  although  this  occurred  unavoidably  in  a  few 
instances.  The  only  possible  ways  that  water  at  body  temperature 
can  stimulate  the  nerve-endings  in  the  mucosa  seem  to  be  (i)  by 
mechanical  pressure,  (2)  by  osmosis,  or  (3)  by  changing  the  chemical 
equilibrium  of  the  content  of  the  stomach.  Cessation  of  the  inhibi- 
tion probably  marks  the  passing  of  the  water  out  of  the  stomach  into 
the  intestine  or  the  addition  of  sufficient  salts  to  prevent  stimu- 
lation by  hypotonicity.  The  greater  inhibitory  action  by  cold 
water  and  by  water  above  the  body  temperature  is  evidently  to 
stimulation  of  the  protopathic  temperature  nerve-endings  in  addi- 
tion to  those  acted  on  by  pressure  and  osmosis. 

It  is  clear  that  the  action  of  water  on  the  stomach  mucosa  is 
in  the  direction  of  inhibition  of  the  hunger  contraction.  How  can 
this  be  reconciled  with  the  view  that  a  glass  of  cold  water  induces 
or  augments  hunger  ?  It  is  to  be  remembered  that  in  these  experi- 
ments the  water  had  no  chance  to  act  on  the  nerve-endings  in  the 
mouth  and  the  esophagus.  The  alleged  action  of  cold  drinks  on 
hunger  and  appetite  is  probably  the  reflex  effects  (cold)  from  the 
mouth  and  esophagus.  In  the  writer's  own  case  a  glass  of  ice  water 
causes  increased  muscular  tonus,  sometimes  even  to  the  point  of 
shivering  and  formication.  This  increased  kinesthetic  sense  prob- 
ably acts  in  the  way  of  Bahnung  for  the  hunger  sensation,  if  it  is 
not  actually  a  part  of  the  hunger  complex.  Cannon  and  Wash- 
burne  suggest  that  the  effect  of  a  cold  drink  on  the  hunger  sensation 
is  due  to  ^'the  power  of  cold  to  induce  contraction  in  smooth 
muscle."  Although  their  meaning  is  not  clear  to  us,  they  probably 
have  in  mind  the  contraction  of  the  stomach  musculature.    This 


NERVOUS  CONTROL  OF  THE  HUNGER  MECHANISM      175 

could  not  come  about  by  the  cold  acting  on  the  stomach  muscula- 
ture directly.  The  reflex  effects  of  cold  water  from  the  mouth  and 
esophagus  are  very  complicated  as  regards  the  stomach,  while  cold 
water  acting  on  the  gastric  mucosa  directly  causes  inhibition,  and 
cooling  the  frog's  stomach  causes  depression  and  atony  in  proportion 
to  the  degree  of  cooling. 

2.  The  action  of  acids. — ^All  acids,  or  liquids  containing  acids, 
including  normal  human  gastric  juice,  cause  inhibition  of  the 
movements  and  the  tonus  of  the  empty  stomach  when  introduced 
directly  into  the  stomach  cavity.  No  acid  has  been  tested  in 
stronger  concentration  than  0.5  per  cent.  The  duration  of  the 
inhibition  is  on  the  whole  directly  proportional  to  the  concentration 
and  the  total  quantity  of  acid  introduced;  200  c.c.  of  0.5  per  cent 
of  HCl  will  usually  inhibit  for  a  period  of  25  to  30  minutes  only. 

This  inhibition  by  acids  can  be  made  evident  during  all  stages 
of  activity  of  the  empty  stomach.  If  the  acid  is  introduced  during 
relative  quiescence  of  the  stomach,  the  appearance  of  the  next 
period  of  hunger  contractions  is  delayed;  if  introduced  during  the 
active  contractions,  these  are  abolished  or  depressed. 

The  duration  of  the  acid  inhibition  is  probably  determined  by 
three  factors,  namely,  (i)  passing  of  the  acid  into  the  duodenum, 
(2)  fixation  and  neutralization  of  the  acid  of  the  mucous  gastric 
secretion,  (3)  neutralization  by  bile  and  intestinal  juice  which  at 
times  pass  into  the  stomach  through  the  dilated  pylorus. 

While  it  is  a  striking  fact  that  gastric  juice  of  full  normal 
acidity  (0.48  to  0.53  per  cent)  and  other  acid  solutions  inhibit  the 
hunger  contractions,  it  does  not  follow  that  a  neutral  or  alkaline 
reaction  in  the  gastric  cavity  is  a  prerequisite  for  these  contractions. 
During  the  strong  contractions  the  stomach  secretes  a  juice  rich  in 
mucin  and  combined  HCl,  but  usually  containing  some  free  HCl. 
After  the  introduction  of  acids  the  contractions  reappear  before 
all  the  acid  has  passed  out  of  the  stomach  or  has  been  completely 
neutrahzed.  And  in  case  Mr.  V.  chews  palatable  food  during  a 
strong  hunger  period,  the  hunger  contractions  reappear  before 
there  is  complete  cessation  of  the  psychic  secretion  of  gastric  juice. 
In  other  words,  the  hunger  contractions  are  not  inhibited  by  weak 


176        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

concentrations  of  acids  in  the  stomach.  A  neutral  or  alkaline 
reaction  of  the  mucosa  is  not  necessary  for  these  contractions.  If 
the  food  is  sufhciently  palatable  and  the  mastication  is  continued 
long  enough,  the  inhibition  produced  reflexly  from  the  mouth  fuses 
with  the  acid  inhibition  from  the  stomach.  If  the  food  is  not 
especially  palatable  or  the  mastication  period  brief,  the  contrac- 
tions may  resume  on  cessation  of  the  chewing  and  then  again  be 
inhibited  for  a  time  during  the  period  of  most  rapid  secretion  of 
the  appetite  gas-tric  juice. 

The  degree  of  inhibition  produced  by  normal  gastric  juice  is  the 
same  as  that  caused  by  an  equal  quantity  of  hydrochloric  acid  of  a 
concentration  equal  to  the  free  acidity  of  the  gastric  juice.  It 
would  thus  seem  that  the  hydrochloric  acid  in  the  gastric  juice 
constitutes  the  stimulus  that  leads  to  the  inhibition. 

This  acid  inhibition  of  the  hunger  contractions  is  of  pecuHar 
interest  in  connection  with  the  neuromuscular  mechanisms  of  these 
hunger  movements  and  the  gastric  movements  in  normal  digestion. 
In  man  the  movements  of  the  stomach  in  digestion  are  not  inhibited 
by  acids  in  the  stomach,  that  is,  at  least  not  by  acids  in  concen- 
trations equal  to  that  of  the  gastric  juice.  The  fact  that  the  inten- 
sity of  movements  of  the  antrum  increases  as  the  gastric  digestion 
advances  may  even  indicate  that  a  certain  degree  of  free  acidity 
facilitates  the  movements  of  digestion.  At  first  it  occurred  to  us 
that  since  acid  in  the  stomach  inhibits  the  hunger  contractions,  but 
not  the  digestion  contractions,  the  mechanisms  involved  in  these 
two  types  of  gastric  activity  are  different,  at  least  as  regards  the 
character  of  the  afferent  impulses  from  the  gastric  mucosa.  But 
on  further  reflection  it  became  apparent  that  this  is  not  necessarily 
the  case,  for  the  digestive  movements  involve  primarily  the 
pyloric  end,  while  the  hunger  movements  (as  studied  by  our  method) 
involve  the  fundus  of  the  stomach.  It  is  possible  that  acid  stimu- 
lation of  the  nerve-endings  in  the  gastric  mucosa  leads,  reflexly,  to  a 
temporary  inhibition  of  the  fundus  and  to  peristalsis  of  the  pyloric 
region  of  the  stomach. 

3.  The  action  of  alkalies. — The  tests  were  made  with  sodium 
carbonate  in  concentrations  varying  from  0.2  to  i.o  per  cent,  and 


NERVOUS  CONTROL  OF  THE  HUNGER  MECHANISM      177 

in  varying  quantities.  In  concentrations  of  0.2  per  cent  or  less  the 
sodium  carbonate  solution  appears  to  have  the  same  influence  on 
the  hunger  contractions  as  equal  quantities  of  water,  that  is,  a 
slight  temporary  inhibition.  This  inhibition  is  evidently  due,  not 
to  the  alkalinity,  but  to  the  bulk  of  the  solution.  In  concentrations 
of  0.2  per  cent  to  i.o  per  cent  the  degree  of  inhibition  produced  is  on 
the  whole  directly  proportional  to  the  concentration  and  the  quan- 
tity of  the  solution  put  into  the  stomach;  200  c.c.  of  i  per  cent  sodium 
carbonate  causes  about  the  same  degree  of  inhibition  as  200  c.c. 
J  per  cent  hydrochloric  acid.  It  is  thus  clear  that  alkalinity  has 
the  same  effect  as  acidity,  only  to  a  less  degree,  both  acids  and 
alkahes  causing  inhibition  without  any  after-effect  of  the  nature  of 
augmentation. 

The  fact  that  0.2  per  cent  sodium  carbonate  has  no  more  effect 
on  the  hunger  movements  than  equal  quantities  of  water  seems  to 
show  that  a  slight  alkalinity  of  the  gastric  mucosa  is  compatible 
with  the  hunger  contractions  of  the  empty  stomach.  It  makes  it 
also  evident  that  the  entrance  of  bile  or  intestinal  juice  into  the 
stomach  will  have  little  or  no  effect  on  these  movements,  while  any 
concentration  that  influences  these  movements  produces  inhibition. 

4.  The  action  of  local  anesthetics. — Solutions  of  some  local 
anesthetics  were  tested  with  the  view  of  determining  whether  the 
sensory  nerves  in  the  gastric  mucosa  play  only  an  inhibitory  role 
in  the  processes  of  gastric  hunger  contractions.  Phenol,  chloreton, 
orthoform,  quinine-urea-hydrochloride,  and  adrenalin  chloride  were 
used  in  quantities  and  concentrations  compatible  with  absolute 
safety  to  Mr.  V.  It  was  not  considered  advisable  to  use  cocaine. 
The  solutions  of  the  drugs  were  introduced  in  quantities  of  100  to 
200  c.c. 

In  the  concentrations  employed  no  specific  action  of  any  of  the 
above  substances  could  be  determined.  For  example,  100  c.c.  of 
phenol  (dilution  i  to  10,000)  has  the  same  effect  as  100  c.c.  of  water, 
that  is,  a  slight  temporary  inhibition.  The  same  applies  to  the 
other  drugs.  No  appreciable  anesthesia  of  the  gastric  mucosa  was 
produced  by  any  of  the  drugs.  It  seems  probable  that  the  solutions 
of  these  drugs  pass  out  of  the  stomach  just  as  rapidly  as  equal 


178        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

quantities  of  water,  and  hence  do  not  remain  long  enough  in  the 
stomach  to  produce  local  anesthesia.  Because  of  the  danger 
attending  the  use  of  local  anesthetics  in  strong  concentrations  in 
the  stomach,  this  work  was  not  carried  further  on  man.  It  seemed, 
however,  that  adrenalin  chloride  introduced  into  the  stomach  in 
considerable  quantities  could  not  be  particularly  injurious.  But 
even  in  large  quantities  (100  c.c.  of  a  dilution  of  1-10,000)  the 
adrenahn  acting  in  the  gastric  cavity  has  no  other  effect  on  the 
hunger  movements  than  equal  quantities  of  water. 

5.  The  action  of  alcoholic  beverages. — Tests  were  made  with  sour 
and  sweet  wines,  beer,  brandy ,f and  pure  alcohol  (diluted).  The 
taking  of  alcoholic  beverages  with  meals  is  a  habit  with  many 
people.  It  is  claimed  by  many  people  that  a  glass  of  wine,  beer,  or 
some  mixture  of  alcohol  taken  before  meals  increases  the  appetite 
(and  possibly  the  hunger) .  The  writer  is  neither  a  total  abstainer 
nor  a  habitual  user  of  alcoholic  beverages.  But  it  is  his  experience 
that  a  glass  of  beer  taken  at  mealtime  seems  to  awaken  or  increase 
appetite.  This  effect  is  rather  immediate  and  therefore  not  due 
solely  to  the  absorption  of  the  alcohol.  Pavlov  has  recorded  an 
instance  from  his  own  experience  where  a  drink  of  wine  seemed  to 
initiate  the  sensation  of  hunger  the  very  minute  the  wine  reached 
the  stomach.  From  inquiries  as  extensive  as  opportunities  have 
permitted  we  are  inclined  to  believe  that  this'^lapparent  augmen- 
tation of  hunger  or  appetite  by  alcoholic  beverages  is  rather  a 
common  experience.^  In  view  of  this  fact,  we  expected  to  find  that 
these  alcoholic  beverages  increased  the  tonus  and  the  contractions 
of  the  empty  stomach,  since  it  is  the  tonus  and  the  contractions  of 
the  empty  stomach  that  give  rise  to  the  hunger  sensation.  To  our 
surprise  the  results  proved  to  be  the  very  opposite.  Wine,  beer, 
brandy,  and  pure  alcohol  (diluted)  introduced  directly  into  the 
stomach  inhibit  the  hunger  contractions  and  the  tonus  of  the 
empty  stomach  instead  of  increasing  them.  This  is  true,  whether 
these  fluids  are  cold  or  at  body  temperature.  If  these  alcoholic 
beverages  are  greatly  diluted  with  water,  a  degree  of  .dilution  can 
be  reached  which  has  the  same  action  on  the  empty  stomach  as 
equal  quantities  of  water,  although  the  specific  beverage  is  readily 


NERVOUS  CONTROL  OF  THE  HUNGER  MECHANISM      179 

detected  when  the  mixture  is  placed  in  the  mouth.  In  no  instance 
have  we  been  able  to  make  out  any  undoubted  augmentation  of 
the  stomach  tonus  and  hunger  contractions  after  the  inhibition 
period.  In  other  words,  alcohoHc  beverages  when  introduced 
directly  into  the  empty  stomach  in  quantities  and  concentrations 
that  directly  affect  the  tonus  and  the  contractions  of  the  stomach 
cause  inhibition,  and  inhibition  only. 

The  pure  alcohol  was  never  used  in  stronger  concentrations 
than  10  per  cent.  The  brandy  was  usually  diluted  one-half  with 
water,  while  the  beer  and  wines  were  put  in  the  stomach  undiluted. 

We  have  seen  that  acids  in  the  stomach  cause  inhibition  of  the 
hunger  contractions.  Pure  alcohol  also  causes  inhibition.  It  is 
therefore  evident  that  the  alcohol  and  acids  are  primarily  respon- 
sible for  the  inhibition  following  the  introduction  of  alcohoHc 
beverages  into  the  empty  stomach.  For  the  sake  of  brevity  we 
may  designate  it  as  ^Hhe  alcohol  inhibition." 

The  duration  of  the  alcohol  inhibition  varies  directly  with  the 
quantity  and  concentration  of  the  beverage  introduced  into  the 
stomach.  Thus  50  to  100  c.c  of  10  per  cent  alcohol  may  inhibit 
the  hunger  contractions  for  i  to  2  hours;  or  if  introduced  during  a 
period  of  relative  quiescence  it  delays  correspondingly  the  onset  of 
the  next  hunger  period.  Inhibition  for  30  to  60  minutes  is  caused 
by  200  c.c.  of  beer.  The  sour  wines  on  the  whole  cause  greater 
inhibition  than  the  sweet  wines,  probably  through  their  acids. 

It  must  be  stated  that  these  alcoholic  beverages  were  put  into 
the  stomach  of  Mr.  V.  and  the  other  subjects,  including  the  author, 
with  their  consent  and  without  any  protest,  resentment,  fear,  or 
disgust  on  their  part,  which  might  account  for  the  stomach  inhibi- 
tion. Mr.  V.  takes  wine  and  beer  occasionally.  At  times  he  bought 
his  own  choice  of  wine  and  beer  and  introduced  into  the  stomach 
the  desired  quantities.  The  effect  on  the  hunger  contractions  was 
always  the  same.  We  are  therefore  dealing  with  a  characteristic 
alcohol  and  acid  inhibition,  and  not  with  a  masked  ''psychic" 
inhibition. 

How  are  these  results  to  be  harmonized  with  the  seeming  stimu- 
lation of  the  appetite  by  alcoholic  beverages  taken  by  the  mouth  ? 


i8o        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

In  the  first  place,  the  local  inhibitory  action  of  alcoholic  beverages 
in  the  gastric  cavity  is  so  marked  and  so  invariable  that  we  feel 
confident  that  this  is  always  the  gastric  effect  of  these  beverages 
in  man,  whether  taken  normally  by  the  mouth  or  introduced  into 
the  empty  stomach  without  coming  in  contact  with  the  mouth  or 
esophagus.  Alcoholic  beverages  can  therefore  not  initiate  or  increase 
hunger,  since  hunger  is  caused  by  the  stomach  contractions,  and 
these  are  inhibited  by  the  alcohol.  Since  most  of  the  alcoholic 
beverages  stimulate  the  end  organs  of  taste  and  smell  as  well  as 
those  of  general  sensibility  in  the  mouth  cavity  and  in  the  esoph- 
agus, it  is  possible  that  this  stimulation  in  some  way  augments  or 
initiates  appetite  for  food.  If  this  is  the  case,  we  have  the  singular 
condition  of  alcoholic  beverages  augmenting  appetite  and  inhibiting 
hunger  at  the  same  time.  There  can  be  little  doubt  that  cerebral 
states,  as  modified  by  training  and  habit,  are  also  factors  in  this 
apparent  action  of  alcoholic  beverages  on  appetite.  It  is  certain 
that  the  individual's  first  taste  of  alcohol,  beer,  or  sour  wines  does 
not  focus  his  attention  on  food  and  eating. 

If  alcohoHc  beverages  in  the  stomach  caused  as  marked  inhibi- 
tion of  the  stomach  movements  in  digestion  as  they  do  in  the 
stomach  movements  in  hunger,  even  moderate  drinking  with  meals 
would  lead  to  acute  indigestion.  As  this  is  not  the  case,  it  is  evident 
that  alcoholic  beverages  affect  the  mechanism  of  these  two  types 
of  movements  differently. 

6.  The  action  of  carbon  dioxide  and  air. — The  action  of  carbon 
dioxide  in  the  cavity  of  the  empty  stomach  was  studied  in  two 
ways:  (i)  by  introduction  of  water  charged  with  CO2,  (2)  by  intro- 
duction of  CO2  gas.  An  excess  of  carbon  dioxide  in  the  blood  of  the 
abdominal  vessels  is  supposed  to  augment  the  tonus  of  the  digestive 
tract,  although  some  recent  work  of  Hooker  throws  doubt  on  this 
interpretation  of  the  stimulating  action  on  intestinal  peristalsis  by 
partial  asphyxia.  An  excess  of  CO2  is  sometimes  found  in  the 
gaseous  contents  of  the  empty  or  partly  filled  stomach.  It  is  known, 
furthermore,  that  carbon  dioxide  in  sufficient  concentration  acts  as 
a  powerful  stimulus  to  the  nerve-endings  in  such  membranes  as 
those  of  the  mouth  and  nose  and  of  the  cornea  and  conjunctiva. 


NERVOUS  CONTROL  OF  THE  HUNGER  MECHANISM      i8i 

« 

Carbon  dioxide  in  the  cavity  of  the  empty  stomach  was  at  first 
considered  a  possible  stimulus  to  the  gastric  hunger  contractions, 
but  this  hypothesis  proved  entirely  erroneous.  So  far  as  the  carbon 
dioxide  in  the  cavity  of  the  stomach  affects  the  hunger  movements, 
the  influence  is  in  the  direction  of  inhibition. 

Water  saturated  with  CO2  under  pressure  has  practically  no 
more  effect  than  similar  quantities  of  pure  water.  It  produces  the 
same  degree  of  temporary  inhibition  without  any  after-effect  of 
augmentation.  As  such  carbonated  water  stimulates  the  nerve- 
endings  in  the  mouth  in  the  characteristic  way,  it  follows  that  the 
nerve-endings  in  the  stomach  are  less  affected  by  CO2  than  are 
the  nerve-endings  in  the  mouth. 

When  the  CO2  is  forced  into  the  stomach  in  the  form  of  gas  and 
under  pressure,  the  results  are  complicated  by  the  mechanical 
action  of  the  gas  in  forcibly  distending  the  walls  of  the  stomach 
and  raising  the  intragastric  pressure,  and  hence  increasing  the 
pressure  on  the  balloon  in  the  fundus.  A  sudden  and  forcible 
distension  of  the  empty  stomach,  no  matter  how  produced,  leads 
to  a  few  strong  contractions.  This  factor  can  be  fairly  well  con- 
trolled by  introducing  the  gas  slowly.  When  this  precaution  is 
taken,  the  empty  stomach  can  be  considerably  distended  with  CO2 
gas,  without  any  marked  effect,  either  on  the  tonus  or  on  the  hunger 
contractions.  But  the  chemical  effect  of  CO2,  so  far  as  it  is  demon- 
strable at  all,  is  in  the  direction  of  inhibition. 

It  will  undoubtedly  occur  to  the  reader  that  this  slight  inhibition 
by  the  CO2  may  be  an  instance  of  '^ psychic"  inhibition  from  the 
distress  of  an  overdistended  stomach.  This  possibility  has  been 
guarded  against.  In  the  first  place,  the  stomach  was  not  distended 
to  the  point  of  painfulness  by  the  carbon  dioxide.  Furthermore, 
the  stomach  cavity  was  irrigated,  so  to  speak,  with  the  gas  without 
raising  the  intragastric  pressure  perceptibly,  by  introducing  the 
inlet  tube  to  the  cardiac  end  and  allowing  the  gas  to  escape  by 
way  of  the  mouth,  or,  in  the  case  of  Mr.  V.,  by  the  open  fistula. 
Under  these  conditions  the  same  slight  inhibitory  effects  were 
recorded  without  signs  of  primary  or  secondary  augmentation.  It 
is  thus  clear  that  so  far  as  carbon  dioxide  in  the  gastric  cavity 


i82        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

affects  the  gastric  tonus  and  hunger  contractions  at  all  the  action 
is  in  the  direction  of  inhibition.  This  is  probably  due  to  the  acid 
stimulation  of  the  nerve-endings  in  the  mucosa. 

The  introduction  of  air  into  the  empty  stomach  has  no  effect 
whatever  on  the  tonus  and  the  hunger  contractions,  provided  the 
stomach  is  not  overdistended  by  the  air,  or  the  air  introduced 
rapidly  and  under  -such  pressure  as  to  cause  sudden  and  forcible 
distension  of  the  stomach  walls.  This  leads  to  a  few  contractions. 
But  the  same  thing  is  produced  by  sudden  inflation  of  the  balloon 
in  the  fundus.  It  is  therefore  purely  mechanical.  Oxygen  in 
greater  concentrations  than  that  of  the  air  has  not  been  tried. 
But  it  is  evident  that  the  20  per  cent  oxygen  of  the  air  acts  neither 
favorably  nor  unfavorably  on  the  hunger  movements. 

The  fact  that  nothing  but  inhibition  is  produced  by  substance 
acting  on  the  gastric  mucosa  suggests  that  this  may  be  in  every 
case  a  ''psychic"  inhibition  masking  any  weak  action  that  may  be 
of  a  positive  or  augmentation  type.  The  very  consciousness  that 
these  substances  were  introduced  into  the  stomach  for  experi- 
mental purposes  might  be  the  primary  element  in  this  possible 
psychic  inhibition. H- That  cerebral  states  may  inhibit  the  gastric 
hunger  movements  is  certain  from  results  both  on  man  and  on 
dogs.  In  one  instance,  when  preparing  to  introduce  200  c.c.  of  0.5 
per  cent  acidic  acid  into  the  stomach  in  the  midst  of  the  period  of 
powerful  hunger  contractions,  Mr.  V.  somehow  thought  that  we 
intended  to  introduce  that  much  concentrated  acid  (or  vinegar). 
As  we  were  going  about  with  the  preparations  it  was  noticed  that 
the  stomach  contractions  suddenly  became  very  feeble.  Mr.  V. 
looked  worried.  We  inquired  if  he  did  not  feel  right,  and  he  asked 
if  we  intended  to  put  all  that  vinegar  into  the  stomach.  ''It  will 
surely  hurt  me,"  he  said.  To  assure  him,  the  author  drank  half 
of  the  acid  himself,  and  then  asked  him  to  take  a  mouthful  of  it. 
Then  he  laughed  and  said,  "Oh,  I  thought  it  was  pure  vinegar." 
In  two  minutes  after  the  mental  stress  and  anxiety  was  over  the 
hunger  contractions  returned  to  their  normal  rate  and  amplitude. 

The  following  facts  speak  against  the  possibiKty  of  the  results 
being  due  to  psychic  inhibition:    (i)  There  was  no  evidence  that 


NERVOUS  CONTROL  OF  THE  HUNGER  MECHANISM      183 

Mr.  V.  or  any  of  the  subjects  were  in  any  way  afraid,  displeased, 
disgusted,  or  impatient  with  the  experiments.  (2)  The  direct 
proportion  between  the  quantity  and  the  concentration  of  the 
substance  introduced  into  the  stomach  and  the  degree  of  inhibition 
produced  is  contrary  to  the  hypothesis  of  a  psychic  inhibition.  The 
displeasure  or  disgust  ought  to  have  been  practically  the  same  on 
introduction  of  o.i  per  cent  and  of  0.5  per  cent  HCl,  of  i  per  cent 
and  10  per  cent  alcohol,  as  in  most  cases  the  subjects  did  not  know 
the  strength  of  the  material  used.  (3)  In  many  cases  the  subject 
was  purposely  deceived  as  to  the  nature  of  the  material,  using 
water  for  acids  and  vice  versa.  The  stomach  reaction  was  invari- 
ably in  accordance  with  the  substance  actually  introduced. 

We  feel  satisfied,  even  on  the  basis  of  the  tests  on  man,  that 
psychic  inhibition  plays  no  role  in  these  results.  But  to  meet  the 
possibility  once  and  for  all,  we  have  repeated  and  confirmed  all  of 
the  above  tests  on  dogs.  The  parallel  on  the  two  series  on  man 
and  dog  is  complete.  May  not  psychic  inhibition  play  a  role  in  the 
tests  on  dogs  ?  It  does  not,  and  for  the  following  reasons:  (i)  The 
dogs  could  not  have  known  either  the  difference  between  the  sub- 
stances introduced  into  the  stomach  or  the  different  concentrations 
of  the  same  substance.  (2)  Tests  were  made  during  sleep  and  with- 
out the  animal  waking  up.  The  results  were  the  same.  (3)  Psychic 
inhibition  of  the  gastric  hunger  movements  in  dogs  is  invariably  of 
much  shorter  duration  than  the  inhibition  caused  by  acids,  alkaHes, 
and  alcoholic  beverages. 

It  is  therefore  clear  that  these  results  on  man  are  fundamental 
facts  in  the  physiology  of  the  stomach  and  not  primarily  dependent 
on  afferent  impulses  that  enter  consciousness. 

5.      INFLUENCE  OF  THE  INHIBITIONS  FROM  THE  GASTRIC  MUCOSA  ON  THE 
FUNDAMENTAL  RHYTHM  OF  THE   GASTRIC  HUNGER  CONTRACTIONS 

During  the  progress  of  this  work  it  soon  became  apparent  that 
these  temporary  inhibitions  described  above  do  not  cut  short  a 
hunger  period,  but  simply  delay  its  culmination.  The  contractions 
that  appear  as  the  inhibition  ceases  are  the  continuation  of  the 
period  temporarily  checked  by  the  inhibition.    They  are  not  the 


i84        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

beginning  of  a  new  period.  When  the  tetanus  stage  of  the  hunger 
period  is  reached  a  stimulation  of  the  gastric  mucosa  sufficiently 
strong  to  cause  prompt  cessation  of  the  contractions  seems  actually 
to  terminate  the  period,  for  when  the  contractions  reappear  they 
are  not  the  incomplete  tetanus  or  strong  and  rapid  contractions 
of  the  culmination  of  the  period,  but  the  feeble  and  slow  movements 
characteristic  of  the  beginning  of  a  period.  By  careful  adjustment 
of  the  quantity  and  strength  of  the  material  introduced  into  the 
stomach  during  the  first  part  of  the  hunger  period  and  by  renewing 
the  inhibition  on  reappearance  of  the  rhythm,  it  is  possible  to 
lengthen  a  30-  to  40-minute  period  into  a  90-  to  120-minute  period. 
In  other  words,  the  motor  mechanisms  of  the  hunger  contractions 
may  be  compared  to  the  spring  of  a  watch.  When  the  spring  is 
wound  up  it  will  run  the  watch  for  a  certain  number  of  hours,  and 
it  makes  no  difference  whether  or  not  these  hours  are  consecutive. 

It  seems  to  us  that  this  fact  has  an  important  bearing  on  the 
question  of  the  primary  stimulus  to  the  hunger  movements.  It 
seems  to  point  to  a  primary  automatism,  peripheral  or  central,  or 
both,  relatively  independent  of  the  condition  of  the  blood  as  well 
as  of  the  afferent  nervous  impulses.  The  fact  speaks  particularly 
strongly  against  the  hypothesis  that  the  primary  stimulus  is  to  be 
sought  in  the  condition  of  the  blood.  For  example,  if  the  primary 
stimulus  is  in  some  condition  of  the  blood,  this  condition  must  be 
present  and  to  a  gradually  increasing  degree  from  1 2 :  30  to  i :  00  p.m. 
to  parallel  a  hunger  period  beginning  at  12:30  p.m.  and  ending  at 
1 :  00  P.M.  And  this  condition  of  the  blood  must  be  absent  from  i :  00 
P.M.  to  1 :45  P.M.,  as  the  stomach  is  relatively  quiescent  during  that 
time.  The  hypothesis  seems  to  'be  rendered  untenable  by  the 
manipulations  which  do  not,  at  least  in  some  cases,  involve  any 
change  in  this  hypothetical  condition  of  the  blood.  The  culmina- 
tion of  the  hunger  period  may  be  delayed  till  1 130  or  1 145  p.m.,  so 
that  the  strongest  hunger  contractions  fall  in  the  time  when  the 
blood  does  not  stimulate  the  gastric  mechanism  in  a  way  to  cause 
hunger  movements. 

But  what  is  the  significance  of  this  inhibition  in  the  normal 
work  of  the  stomach  ?    The  inhibition  of  the  hunger  contractions 


NERVOUS  CONTROL  OF  THE  HUNGER  MECHANISM      185 

by  mechanical  and  chemical  stimulation  of  the  gastric  mucosa  in 
the  normal  person  prevents  the  appearance  of  these  contractions 
during  the  period  of  gastric  digestion.  This  negative  control  of  the 
hunger  movements  from  the  stomach  cavity  is  obviously  a  useful 
co-ordination.  The  primary  or  actual  stimulus  to  the  hunger  con- 
tractions is  therefore  to  be  sought  in  the  vagus  tonus,  in  some 
condition  of  the  blood,  or  in  a  primary  automatism  of  the  gastric 
neuromuscular  mechanism.  We  have  some  evidence  that  the 
latter  is  the  essential  factor  and  that  extrinsic  nerves  and  the 
condition  of  the  blood  only  modify  the  primary  automatism.  If 
this  is  the  case  the  hunger  contractions  ought  to  appear  as  soon  as 
the  stomach  is  empty  of  food  or  other  substances  capable  of  stimu- 
lating the  nerve-endings  in  the  mucosa.  We  should  also  expect 
these  contractions  to  be  more  or  less  continuous  as  long  as  the 
stomach  is  empty,  at  least  in  young  and  vigorous  individuals,  and 
when  the  condition  of  the  individual  as  a  whole  does  not  lead  to 
increased  activity  of  the  extrinsic  inhibitory  nerves  (splanchnics) . 
On  this  hypothesis  the  gradual  tonus  contraction  of  the  gastric 
fundus  pari  passu  with  the  progress  of  the  gastric  digestion  repre- 
sents the  algebraic  sum  of  the  inherent  automatism  and  the 
inhibitory  effects  from  the  gastric  cavity.  A  gradual  fatigue  of 
the  inhibitory  mechanisms  is  probably  also  a  factor,  as  we  have 
abundant  evidence  (in  man  and  dog)  of  such  ''escape"  of  the 
stomach  from  inhibitory  nervous  processes. 

We  should  probably  look  for  the  closest  parallelism  between 
the  gastric  hunger  contractions  and  the  absence  of  stimulation 
of  the  gastric  mucosa  in  infants  and  young  children,  that  is,  before 
cerebral  (and  possibly  gastric)  habits  relative  to  feeding  have  been 
established.  We  have  made  a  close  study  of  a  healthy  (bottle-fed) 
infant  touching  this  point.  It  is  well  known  that,  other  things 
being  equal,  the  more  food  put  into  the  stomach  the  longer  is  the 
time  required  for  the  completion  of  gastric  digestion.  If  this 
infant  (five  months  old)  is  given  only  4  ounces  of  food  he  calls  for 
more  after  about  2  hours.  If  he  is  given  7  to  8  ounces  of  the  same 
food  the  call  for  more  food  is  delayed  for  3  to  4  hours.  If  he  is 
given  5  ounces  of  the  food  at  6 :  00  p.m.  he  nearly  always  wakes  up 


1 86        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

and  calls  for  more  at  12:00  or  1:00  o'clock,  while  if  he  is  given 
as  much  food  as  he  will  take  (7 J  to  8 J  ounces)  at  6:00  p.m.  he 
rarely  wakes  up  and  calls  for  food  until  3 :  00  or  5 :  00  o'clock  the 
following  morning.  There  is  evidently  a  close  parallel  between 
the  time  of  the  emptying  of  the  stomach  and  the  appearance  of  the 
hunger  contractions.  The  more  frequent  calls  for  food  during 
the  day  are  obviously  due  to  the  fact  that  the  gastric  hunger  con- 
tractions must  reach  a  certain  degree  of  intensity  before  they  cause 
the  soundly  sleeping  infant  to  wake  up.  This  is  certainly  true  in 
the  case  of  dogs.  A  dog  may  sleep  on  peacefully  and  quietly  during 
gastric  hunger  contractions  of  moderate  intensity.  When  these 
contractions  become  very  intense  the  dog  moves  or  moans  in  his 
sleep  and  sometimes  wakes  up. 

While  we  have  made  no  observations  on  the  action  of  acids, 
alkalies,  and  alcoholic  beverages  on  the  gastric  movements  of 
digestion  in  man,  it  is  well  kiiown  that  these  substances  do  not 
inhibit  these  movements  to  the  extent  that  they  inhibit  the  hunger 
contractions.  The  movements  of  digestion  are  primarily  concerned 
with  the  pyloric  region,  while  the  hunger  contractions  involve  the 
cardiac  and  fundus  region.  Evidently  these  two  regions  of  the 
stomach  react  differently  to  local  chemical  stimulation  of  the  gastric 
mucosa. 

In  view  of  the  fact  that  acids  as  well  as  normal  gastric  juice 
inhibit  the  gastric  hunger  contractions,  one  might  expect  that 
persons  having  gastric  hypersecretion  should  experience  little  or 
no  true  hunger  sensations  or  pangs  of  gastric  origin.  At  the  same 
time  we  must  consider,  in  cases  of  prolonged  hypersecretion,  the 
possibility  of  a  readjustment  of  such  a  character  that  the  acid 
stimulation  of  the  mucosa  causes  less  inhibition  than  is  the  case  in 
the  normal  stomach. 

III.      INHIBITORY  REFLEXES   FROM  THE  GASTRIC  MUCOSA  IN  DOGS 
AND   OTHER  ANIMALS 

The  work  on  man  led  to  the  conclusion  that  any  substance 
capable  of  stimulating  the  nerve-endings  in  the  gastric  mucosa 
causes  inhibition  of  the  tonus  and  hunger  contractions,  and  inhibi- 


NERVOUS  CONTROL  OF  THE  HUNGER  MECHANISM      187 

tion  only,  as  there  is  no  evidence  of  any  increase  in  the  gastric  tonus 
or  hunger  contractions  following  the  primary  inhibition.  The 
experiments  on  dogs  were  undertaken  primarily  to  determine  the 
character  of  this  reflex,  that  is,  whether  central,  or  local,  or  both. 
The  liquids  were  introduced  into  the  stomach  through  the  fistula 
by  means  of  a  soft  rubber  tube,  so  that  swallowing  acts  and  the 
stimulation  of  nerve-endings  in  the  mouth,  the  pha'r3aix,  and  the 
esophagus  were  completely  eliminated. 

I.  Action  of  water,  acids,  alkalies,  and  alcoholic  beverages. — The 
observations  were  made  on  six  dogs  with  all  the  extrinsic  gastric 
nerves  intact;  on  six  dogs  with  the  splanchnic  nerves  cut;  and  on 
four  dogs  with  complete  section  of  both  of  the  vagi  and  the  splanch- 
nic nerves.  The  results  on  the  normal  dogs  are  practically  identical 
with  those  on  man.  Gastric  juice  (human,  canine),  weak  acids  and 
alkahes,  brandy,  wines,  and  beer  introduced  directly  into  the 
empty  stomach  during  hunger  contractions  produce  immediate 
inhibition  of  the  gastric  tonus  and  contractions.  Thus  the  same 
quantity  of  gastric  juice  or  wine  seems  to  cause  more  prolonged 
inhibition  in  dogs  showing  the  type  I  than  in  the  dogs  showing 
type  III  hunger  rhythms.  The  duration  of  these  inhibitions  can 
best  be  studied  in  the  dogs  showing  types  II  and  III  of  hunger 
contractions,  as  these  two  forms  are  practically  continuous,  so 
that  the  errors  from  spontaneous  periods  of  relative  quiescence 
are  eliminated.  In  normal  dogs  showing  contractions  of  types  II 
and  III,  25  c.c.  gastric  juice  or  0.5  per  cent  HCl  usually  causes 
complete  inhibition  for  20  to  30  minutes.  The  return  of  the  hunger 
contractions  is  always  gradual.  In  like  manner,  25  c.c.  of  beer  will 
inhibit  for  15  to  25  minutes.  In  one  case  50  c.c.  of  beer  caused 
complete  inhibition  for  one  hour. 

If  these  substances  are  introduced  into  the  stomach  of  dogs 
during  a  period  of  relative  quiescence  and  tonus  relaxation  the  only 
effect  appears  to  be  a  still  greater  tonus  relaxation  and  prolongation 
of  the  quiescent  period.  In  some  cases  one  or  two  hunger  con- 
tractions follow  immediately  on  introducing  the  material  into 
the  stomach.  We  are  inclined  to  attribute  these  contractions 
to  the  mechanical  distension  of  the  stomach  wall  rather  than  to 


1 88        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

stimulation  of  nerve-endings  in  the  mucosa.  This  phenomenon  was 
never  observed  when  the  stomach  was  in  strong  tonus  and  hunger 
contractions. 

2.  Action  of  carbon  dioxide. — The  influence  on  the  hunger  con- 
tractions of  CO2  in  the  stomach  cavity  is  the  same  in  dog  and  man. 
The  experiments  on  dogs  were  made  with  water  saturated  with  CO2 
and  with  CO^  gas.  When  the  gas  was  employed,  at  times  enough  of 
it  was  passed  into  the  stomach  via  the  fistula  to  cause  escape  of 
the  gas  through  the  esophagus.  The  water  saturated  with  CO2  has 
practically  the  same  action  as  ordinary  water,  that  is,  a  slight 
temporary  inhibition  without  any  after-effect  of  the  nature  of 
increased  tonus  or  contractions.  This  is  true  whether  the  car- 
bonated water  is  introduced  during  active  hunger  contractions  or 
during  relative  quiescence.  The  CO2  gas  usually  initiates  some 
contractions  if  introduced  into  the  stomach  during  a  period  of 
quiescence.  This  is  evidently  due  to  mechanical  distension  of  the 
stomach  walls  and  not  to  chemical  stimulation  of  nerve-endings 
in  the  mucosa.  If  the  empty  stomach  is  in  vigorous  tonus  and 
hunger  contractions  the  CO2  gas  causes  a  slight  temporary  inhibi- 
tion without  any  stimulating  after-effect.  This  temporary  in- 
hibition is  in  all  probability  due  to  a  weak  acid  stimulation  in  the 
nerve-endings  in  the  mucosa. 

3.  Effects  of  complete  section  of  the  splanchnic  nerves. — ^The 
inhibition  of  the  gastric  tonus  and  hunger  contractions  by  acids, 
alkalies,  alcohol,  etc.,  in  the  stomach  cavity  persists  after  section 
of  the  splanchnic  nerves,  but  it  is  on  the  whole  less  complete  and 
of  shorter  duration  than  in  dogs  with  all  the  extrinsic  gastric  nerves 
intact.  This  applies  to  all  substances  used  in  this  series  of  experi- 
ments. When,  as  in  the  present  series,  the  test  with  each  substance 
is  repeated  at  least  ten  times  on  each  animal,  some  variation  in  the 
intensity  and  duration  of  the  inhibition  appears.  That  is  to  be 
expected,  because  the  degree  of  inhibition  depends  on  several 
variable  factors,  such  as  the  excitability  of  the  nerve-endings  in 
the  mucosa,  the  excitability  of  the  Auerbach  plexus  and  of  the 
central  nervous  system,  the  tonus  of  the  stomach,  etc.  It  is  there- 
fore true  that  the  most  pronounced  inhibition  observed  after  section 


NERVOUS  CONTROL  OF  THE  HUNGER  MECHANISM   189 

of  the  splanchnic  nerves  may  be  as  marked  as  the  feeblest  inhibition 
obtained  in  the  normal  dogs.  But  when  all  the  results  in  the  two 
series  of  dogs  are  compared  there  is  no  question  but  that  section  of 
both  splanchnic  nerves  diminishes  the  inhibition  following  chemical 
stimulation  of  the  gastric  mucosa  by  acids,  alkalies,  alcohol,  etc. 

Several  explanations  of  this  fact  suggest  themselves,  (i)  Since 
section  of  the  splanchnic  nerves  in  dogs  increases  on  the  whole  the 
tonus  and  the  hunger  contractions  of  the  empty  stomach,  the 
diminished  inhibition  may  be  due  to  this  greater  vigor  of  the 
stomach  rather  than  cutting  the  efferent  path  of  a  long  reflex. 
We  do  not  think  that  this  is  the  main  or  important  factor,  because 
the  typical  marked  inhibition  is  obtained  in  normal  dogs,  even 
when  the  stomach  shows  as  vigorous  tonus  and  hunger  contractions 
as  the  maximum  shown  by  dogs  with  the  splanchnic  nerves  severed. 
Moreover,  the  inhibition  is  still  incomplete  in  splanchnetomized 
dogs  that  show  relatively  feeble  hunger  contractions.  (2)  The 
substances  stimulate  afferent  vagi  nerve-endings  in  the  mucosa, 
and  the  afferent  vagi  impulses  via  conscious  or  subconscious  cen- 
ters finally  stimulate  the  efferent  inhibitory  neurones  in  the  splanch- 
nic system.  It  is  well  known  that  the  vagi  carry  afferent  fibers 
from  the  stomach  mucosa  and  that  the  splanchnic  nerves  carry 
inhibitory  fibers  to  the  stomach.  The  present  experiments  give 
the  first  intimation  that  the  afferent  vagus  and  the  efferent  splanch- 
nic systems  are  so  intimately  associated  in  gastric  motor  reflexes. 
It  is  possible  that  the  reflex  also  involves  the  adrenal  glands,  so 
that  the  inhibition  mentioned  above  is  to  be  accounted  for,  in 
part,  by  the  depressor  action  of  an  increased  output  of  epinephrin. 

4.  Efect  of  section  of  the  vagi  nerves  and  of  the  vagi  and  the 
splanchnic  nerves. — When  all  the  records  are  compared  it  appears 
that  section  of  the  vagi  nerves  alone  or  section  of  both  the  splanchnic 
and  the  vagi  nerves  diminishes  the  inhibitory  reflex  from  the  gastric 
cavity  on  the  whole  more  than  does  the  section  of  the  splanchnic 
nerves  alone.  A  fact  of  greater  importance,  however,  is  the  per- 
sistence of  the  reflex  after  complete  isolation  of  the  stomach  from 
the  central  nervous  system.  The  inhibition  is  therefore  a  primary 
local  reflex.    The  decrease  of  the  inhibition  after  the  vagi  section 


IQO        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

may  involve  two  mechanisms.  It  is  well  known  that  the  vagi  con- 
tain some  efferent  inhibitory  fibers  to  the  stomach  motor  mechan- 
ism, and  these  may  be,  together  with  the  splanchnic  inhibitory 
fibers,  involved  in  the  long  inhibitory  reflex.    But  since  the  gastric 


II 


,_„^^}i!^'^''^-"Ut»UI. 


^^^^^^^^^^^^^^^^^^^ 


yr      '     y\mY\m0f^\'Ml^^ 


:UH,M,WW^H^^ 


Fig.  20. — I.  Tracings  from  empty  stomachs  of  dogs.  A,  normal  dog;  B,  dog 
with  both  splanchnic  nerves  cut;  X,  introduction  of  25  c.c.  0.5  per  cent  HCl  into 
the  stomach;  showing  less  complete  inhibition  of  the  hunger  contractions  by  acid 
in  the  stomach  after  section  of  the  splanchnic  nerves.    One-third  original  size. 

II.  Tracings  from  the  empty  stomach  of  dogs.  A,  normal  dog;  B,  dog  with 
section  of  the  vagi  and  splanchnic  nerves;  X,  introduction  of  12  c.c.  of  brandy-|-i2  c.c. 
of  water  into  the  stomach;  showing  less  complete  inhibition  by  alcohol  in  the  case  of 
the  stomach  isolated  from  the  central  nervous  system.    One-half  original  size. 

tonus  fibers  in  the  vagi  and  the  gastric  inhibitory  fibers  in  the 
splanchnic  nerves  are  practically  antagonistic,  it  is  highly  probable 
that  afferent  influences  leading  reflexly  to  the  stimulation  of  the 


NERVOUS  CONTROL  OF  THE  HUNGER  MECHANISM      191 

inhibitory  neurones  lead  at  the  same  time  to  the  inhibition  of  the 
tonus  or  motor  neurones. 

The  reader  may  object  that  we  are  now  discussing  interferences 
that  do  not  necessarily  follow  from  the  facts  so  far  at  hand.  The 
facts,  in  brief,  are  these.  The  inhibition  of  the  tonus  and  the  con- 
traction of  the  empty  stomach  by  stimulation  of  the  gastric  mucosa 
persist  after  isolating  the  stomach  from  the  central  nervous  system, 
but  the  inhibition  is  diminished  in  intensity  and  duration  after 
section  of  the  splanchnic  nerves,  and  somewhat  more  so  after 
section  of  the  vagi  nerves.  It  has  been  shown  that  section  of  the 
vagi  leaves  the  stomach  on  the  whole  permanently  hypotonic, 
except  during  prolonged  starvation,  although  there  seems  to  be  a 
gradual  improvement  in  the  efficiency  of  the  local  tonus  mechanism . 
Is  it  not  possible  that  the  lessened  inhibition  after  the  vagi  lesion 
is  due  to  the  depression  of  the  excitability  of  the  local  afferent 
nerve-endings  in  the  mucosa  or  depression  of  the  local  reflex  center 
similar  to  the  tonus  depression  ?  Our  experiments  do  not  exclude 
this  possibility,  but  the  results  on  the  dogs  with  only  the  splanchnic 
nerves  severed  show  conclusively  that  it  is  not  the  sole  factor;  for 
in  these  dogs  there  is  no  gastric  hypotonus,  and  yet  the  inhibition 
from  the  gastric  mucosa  is  diminished. 

Another  possibility  has  occurred  to  us.  When  the  same  quantity 
(25  to  50  c.c.)  of  acids,  alkalies,  or  alcoholic  beverages  is  introduced 
into  the  stomach  in  tonus  and  into  a  stomach  in  hypotonus,  it 
seems  likely  that  the  solution  will  come  in  contact  with  more  of  the 
mucous  membrane  in  the  tonic  than  in  the  atonic  stomach.  This 
might  result  in  less  inhibition  in  the  case  of  atonic  stomach  from  the 
mere  fact  of  stimulation  of  less  of  the  afferent  nervous  mechanism. 
We  have  tested  this  possibility  by  introducing  a  greater  quantity 
of  the  respective  solutions  in  the  hypotonic  stomach.  But  if  25  c.c. 
of  acid  or  beer  fail  to  produce  complete  inhibition,  50  c.c.  of  the 
same  liquid  usually  also  fail.  This  is  to  be  noted,  however,  that 
the  depression  of  inhibition  following  splanchnic  and  vagi  section  is 
most  marked  for  a  week  or  two  after  these  nerve  lesions  are  made, 
and  there  is  a  distinct  tendency  in  the  efficiency  of  the  local  reflex 
pari  passu  with  the  improvement  of  the  local  tonus  mechanism. 


192        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

This  is  probably  an  instance  of  readjustment  of  local  reflex 
mechanisms  to  a  fair  degree  of  efficiency  in  the  absence  of  central 
tonus  and  accessory  central  long  reflexes. 

The  experiments  on  man  and  on  normal  dogs  led  to  the  con- 
clusion that  contractions  of  the  empty  stomach  cannot  be  induced 
by  the  stimulation  of  the  gastric  mucosa — that  such  stimulation 
causes  inhibition  only.  It  was  noted  that  one  or  two  contractions 
occasionally  follow  immediately  on  the  introduction  of  these  liquids 
into  the  stomach,  but  it  seemed  probable  that  these  contractions 
were  due  to  the  mechanical  distension  of  the  stomach  walls  rather 
than  to  the  chemical  or  mechanical  stimulation  of  the  nerve-endings 
in  the  mucosa.  These  initial  contractions  following  the  introduc- 
tion of  acids,  alkalies,  or  alcoholic  beverages  into  the  stomach 
occur  more  frequently  in  the  hypotonic  stomach  isolated  from  the 
central  nervous  system.  This  is  true  even  when  special  care  is 
taken  to  introduce  the  substance  slowly  so  as  not  to  cause  sudden 
distension  of  the  stomach  walls.  I  am  not  yet  satisfied  that  this 
primary  motor  response  is  actually  due  to  stimulation  of  nerve- 
endings  in  the  mucosa.  If  it  is,  there  must  be  in  the  mucosa  a  few 
afferent  nerve-endings  of  the  excitatory  type;  but  the  afferent 
inhibitory  nerve-endings  are  so  much  more  numerous  that  the 
influence  of  the  former  group  is  completely  submerged  by  the 
latter,  except  occasionally,  when  the  stomach  is  hypotonic,  or  else 
local  afferent  nerve-endings  in  the  mucosa  are  all  of  one  type; 
but  the  type  of  reflex  produced  by  this  stimulation  may  depend 
in  part  on  the  tonus  condition  of  the  reflex  centers  (Auerbach 
plexus) . 

The  local  and  long  reflex  mechanisms  governing  the  tonus  and 
the  hunger  contractions  of  the  empty  stomach  demanded  by  the 
foregoing  work  on  dogs  are  diagrammatically  represented  in  Fig.  21 . 
It  may  be  noted  that  this  diagram  is  not  intended  to  represent  all 
the  afferent  gastric  nerve  components,  such  as  those  acting  in 
various  ways  on  consciousness,  on  the  vasomotor  centers,  etc. 
The  adrenal  glands  are  indicated  simply  as  a  possible  factor, 
because  conclusive  data  have  not  yet  been  obtained  on  that  point. 


NERVOUS  CONTROL  OF  THE  HUNGER  MECHANISM      193 


Rogers  found  that  water,  weak  alcohol  (10  per  cent),  weak 
acids  (0.2  to  0.4  per  cent  HCl),  sugar  solutions,  fruit  juices,  etc., 
introduced  directly  into  the  stomach  in  rabbits  cause  temporary 
inhibition  of  the  hunger  contrac- 
tions, but  have  no  apparent  effect 
on  the  digestion  peristalsis  when 
introduced  in  the  filled  stomach. 
In  the  guinea-pig  Dr.  King  failed 
to  obtain  definite  inhibition  of 
the  hunger  contractions  by  chemi- 
cal stimulation  of  the  mucosa. 
In  these  experiments  it  is  possible 
that  the  stomach  was  not  com- 
pletely empty,  hence  the  resist- 
ance to  local  chemical  stimulation, 
as  Rogers  and  Hardt  found  that 
even  in  man  the  tonus  rhythm 
of  the  fundus  that  is  present 
during  the  digestion  peristalsis  is 
much  more  resistant  to  inhibition 
from  chemical  stimulation  of  the 
mucosa  than  is  the  very  same 
tonus  contraction  in  the  empty 
stomach  of  the  same  individual. 

Water  and  weak  acids,  etc., 
introduced  directly  into  the  empty 
crop  of  pigeons  cause  inhibition  of 
the  hunger  contractions.  In  the 
bullfrog  water,  weak  acids,  weak 
alkalies,  etc.,  inhibit  temporarily 
both  the  hunger  contractions  and 
the  digestion  peristalsis.  In  the 
frog  the  inhibition  from  the  gastric 

mucosa  is  much  more  marked  than  that  produced  by  chemical 
stimulation  of  the  nerve-endings  in  the  mouth  (Patterson). 


Fig.  21. — Diagram  to  represent  the 
local  and  the  long  reflex  mechanisms 
involved  in  the  inhibition  of  the  gastric 
tonus  and  the  hunger  contractions  from 
stimulation  of  the  gastric  mucosa.  A , 
adrenal  gland;  B,  gastric  mucosa;  C, 
stomach  musculature;  D,  Auerbach's 
plexus;  E,  local  afferent  neurones  from 
the  gastric  mucosa  to  Auerbach's  plexus 
(these  neurones  are  predominantly  in- 
hibitory) ;  H,  tonus  or  motor  neurones 
to  the  stomach  via  the  vagi;  L,  afferent 
neurones  in  the  vagi  from  the  gastric 
mucosa;  P,  neurones  in  the  splanchnic 
nerves;  +=  stimulation;  —  =  inhibition. 


194        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

The  inhibitory  reflexes  from  the  gastric  mucosa  to  the  gastric 
musculature  are  thus  present  in  all  animals  so  far  studied.  The 
mechanism  is  probably  present  in  all  animals  with  a  well-developed 
stomach.  But  the  efficiency  of  the  reflexes  varies  in  different  spe- 
cies, and  in  the  same  species  or  individuals  they  vary  with  the 
condition  of  the  stomach  (filled  or  empty). 


m:umM> 


Fig.  22. — a,  lo  c.c.  of  0.25  per  cent  hydrochloric  acid  put  into  the  rabbit's  stom- 
ach during  normal  digestion  peristalsis;  b,  10  c.c.  of  0.25  per  cent  hydrochloric  acid 
put  into  the  stomach  of  a  hungry  rabbit;  c,  10  c.c.  of  water  put  into  the  stomach  of  a 
hungry  rabbit;  d,  10  c.c.  of  10  per  cent  alcohol  put  into  the  stomach  of  a  hungry  rab- 
bit.   Note  the  inhibitory  efifect  of  these  solutions  on  the  hunger  movements  (Rogers) . 


ly.      INHIBITORY  REFLEXES  FROM  THE   INTESTINAL  MUCOSA 
TO  THE  EMPTY  STOMACH 

We  have  seen  that  the  tonus  and  contractions  of  the  empty 
stomach  are  temporarily  inhibited  by  stimulation  of  nerves  in  the 
mouth,  in  the  esophagus,  and  in  the  gastric  mucosa  itself.  Can 
the  tonus  and  hunger  contractions  of  the  empty  stomach  be 


NERVOUS  CONTROL  OF  THE  HUNGER  MECHANISM      195 

influenced  reflexly  by  stimulation  of  the  intestinal  mucosa?  The 
answer  to  this  question  might  explain  the  diminution  or  abolition 
of  hunger  by  the  introduction  of  chyme  into  the  intestine.  If  such 
reflex  relations  exist,  it  is  dtvious  that  the  intestinal  mucosa  must 
he  an  important  factor  in  the  control  of  the  gastric  tonus  and  hunger 
mechanism. 

Boldyreff  reports  that  acids  in  the  intestine  inhibit  the  periodic 
activity  of  the  empty  stomach.  The  inhibition  was  not  obtained 
by  water  or  alkaline  solutions.  In  fact,  Boldyreff  appears  to  imply 
that  the  periodic  contractions  of  the  empty  stomach  may  be 
initiated  by  the  introduction  of  a  solution  of  0.3  per  cent  NaaCOa 
into  the  intestine.  He  therefore  concludes  that  the  reflex  inhibition 
is  due  to  an  acid  stimulation  of  nerves  in  the  intestinal  mucosa. 
If  chemical  stimulation  of  the  intestinal  mucosa  induces  increased 
intestinal  tonus  and  contractions,  we  should  expect  the  increased 
motility  of  the  intestines  to  cause  some  inhibition  both  of  the 
digestion  peristalsis  and  the  hunger  contractions  of  the  stomach 
according  to  the  interesting  theory  of  gastero-intestinal  co-ordination 
recently  advanced  by  Alvarez. 

In  our  work  we  used  24  young  female  dogs.  Intestinal  fistulas 
were  made  by  Abbe's  lateral  anastomosis  in  the  first  loop  of  the 
small  intestine  below  the  pancreas,  the  cephalad  end  being  sutured 
into  the  abdominal  wall  and  left  open  to  the  exterior.  The  gastric 
fistula  was  made  after  recovery  from  the  first  operation. 

In  another  group  of  dogs  a  Tiery  fistula  was  made,  but  no  gas- 
tric fistula,  the  recording  apparatus  being  introduced  into  the 
stomach  through  the  esophagus. 

In  the  third  group  the  gastric  fistula  was  made  near  the  pyloric 
end  of  the  stomach.  Through  this  fistula  a  small  stomach  tube  was 
passed  through  the  pylorus  into  the  small  intestine  for  varying 
distances.  This  tube  was  kept  in  the  gut  throughout  the  experi- 
ment for  the  introduction  of  the  liquids  into  the  intestine.  The 
recording  balloon  was  passed  into  the  stomach  either  through  the 
gastric  fistula  or  through  the  esophagus. 

In  the  last  group  of  dogs  the  vagi  and  splanchnic  nerves  were 
cut,  and  after  recovery  from  the  operation,  gastric  fistula   was 


196        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

established  in  the  antrum  pylori.  In  all  tests  on  this  group  the 
fluids  were  introduced  into  the  intestine  by  means  of  a  tube 
passed  through  the  pylorus,  and  the  stomach  balloon  was  passed 
down  through  the  esophagus. 

The  following  solutions  were  introduced  into  the  intestine  in 
10  c.c.  quantities,  in  most  cases  at  body  temperature:  normal 
gastric  juice  (dog  and  man);    10  per  cent  Witte's  peptone  in  0.2 


/ 

""  ^i/jvi'''^?*'''%  *"    '/  ^  i  '^iiij^4.yM0i^0^f 

Fig.  23. — Tracings  of  the  empty  stomach  of  dogs.  A,  a,  mechanical  stimulation 
of  intestinal  mucosa  (gently  moving  a  rubber  tube  in  the  lumen) ;  b,  lo  c.c.  water  intro- 
duced into  the  intestine;  c,  10  c.c.  of  0.3  per  cent  NaaCOs  introduced  into  the  intes- 
tines; B,  a,  10  c.c.  of  10  per  cent  peptone  in  0.2  per  cent  HCl  introduced  into  intestine; 
b,  10  c.c.  fresh  milk  introduced  into  the  intestine;  showing  temporary  inhibition  of 
tonus  and  hunger  contractions  of  the  empty  stomach  by  mechanical  and  chemical 
stimulation  of  the  intestinal  mucosa. 


per  cent  HCl;  pepsin  in  0.2  per  cent  HCl;  hydrochloric  acid 
(o.i  per  cent  to  0.5  per  cent);  saturated  H2CO3  solution;  neutral 
olive  oil;  fresh  milk;  water;  mechanical  stimulation  of  the  intes- 
tinal mucosa  (glass  rod  or  rubber  tube) . 

When  the  vagi  and  splanchnic  nerves  are  intact  all  mechanical 
and  chemical  stimulations  of  the  intestinal  mucosa  cause  inhibition 
of  the  gastric  tonus  and  hunger  contractions.  The  effect  of  a 
purely  mechanical  stimulation  (rubbing  the  mucosa  with  a  glass 


NERVOUS  CONTROL  OF  THE  HUNGER  MECHANISM      197 

rod  or  rubber  tube)  is  the  most  transitory.  In  general  pure  gastric 
juice  and  the  0.5  per  cent  HCl  cause  the  longest  inhibition.  The 
acid  peptone  solution  followed  these  closely.  The  weaker  acids 
produced  inhibition  of  less  duration.  Saturated  carbonic  acid 
solution  did  not  give  quite  so  distinct  an  inhibition  as  the  other 
acids.     Inhibition  with  pure  gastric  juice  and  the  acid  peptone 


JV\ 


'w>«|i»WwM>''0»*»''  V 


Fig.  24. — Tracing  showing  tonus  and  hunger  contractions  of  the  empty  stomach 
of  dogs.  A,  10  c.c.  of  gastric  juice  introduced  into  small  intestine  at  a;  B,  10  c.c. 
0.5  per  cent  HCl  introduced  into  small*  intestine  at  a;  C,  10  c.c.  i  per  cent  NaaCOj 
introduced  into  small  intestine  at  a;  showing  reflex  inhibition  of  the  tonus  and  the 
hunger  contractions  of  the  empty  stomach  by  chemical  stimulation  of  intestinal 


mixture  varied  in  duration  from  3  to  20  minutes,  depending  appar- 
ently largely  on  the  condition  of  the  animal  at  the  time.  The 
sodium  carbonate  solution  caused  inhibition  of  less  duration  than 
acid  mixtures,  but  of  longer  duration  than  the  water  or  the  neutral 


1 98        CONTROL  OF  HUNGER' IN  HEALTH  AND  DISEASE 

mixtures  in  generaL  However,  the  longest  inhibition  obtained  in 
any  one  experiment  was  produced  by  lo  c.c.  of  milk  in  the  gut. 
In  this  case  the  inhibition  lasted  30  minutes.  Ordinarily  neutral 
solutions  produced  a  longer  inhibition  than  the  mechanical  stimu- 
lation by  moving  the  soft  rubber  tube  in  the  intestinal  fistula. 

In  the  animals  with  the  vagi  and  splanchnic  nerves  severed  the 
substances  named  above  still  caused  reflex  inhibition  of  the  empty 
stomach  from  the  intestinal  mucosa,  but  the  latent  period  of  the 
inhibition  was  greatly  prolonged,  the  degree  of  the  inhibition  less, 
and  the  duration  of  it  much  shorter  than  in  the  normal  animals. 

It  is  therefore  clear  that  this  inhibition  of  the  tonus  and  mechan- 
ical stimulation  of  the  intestinal  mucosa  involve  both  long  or 
central  and  short  or  local  reflex  paths,  a  situation  similar  to  that 
found  in  the  gastric  mucosa  itself. 

We  may  conclude,  then,  that:  (i)  Gastric  juice,  chyme,  acids, 
alkalies,  water,  milk,  and  oil  introduced  into  the  small  intestine 
inhibit  gastric  hunger  contractions  and  gastric  tonus  for  varying 
periods.  (2)  This  inhibition  is  due  partly  to  mechanical,  partly 
to  chemical,  stimulation  of  the  intestinal  mucosa.  The  chemical 
stimulation  produces  the  greatest  effect.  (3)  This  inhibition  takes 
place  primarily  by  the  ''long"  or  central  reflex  path,  but  ''short" 
or  local  reflex  paths  in  Auerbach's  plexus  are  also  involved 
(Elsesser) . 

The  precise  role  of  these  reflexes  in  the  control  of  the  gastric 
hunger  mechanism  in  the  normal  animal  must  be  determined  by 
further  investigation.  They  are  probably  factors  in  the  diminution 
or  absence  of  hunger  in  cases  of  enteritis,  intestinal  obstruction, 
constipation,  appendicitis,  and  gallstones. 


CHAPTER  XII 

THE  NERVOUS  CONTROL  OF  THE  HUNGER  MECHANISM 

(Continued) 

I.      INHIBITION   OF  HUNGER  BY  SMOKING  AND   BY  PRESSURE 
ON  THE  ABDOMEN 

It  is  generally  held  to  be.  true  that  smoking  shortly  before  a 
meal  leads  to  depression  of  hunger  and  appetite.  It  is  also  a 
common  belief  that  strong  pressure  on  the  abdomen  (''tightening 
the  belt")  decreases  or  relieves  the  hunger  sensation,  at  least 
temporarily.  We  are  now  in  position  to  test  the  correctness  of  these 
beliefs  by  decisive  experiments  as  regards  the  influence  of  these 
measures  on  the  objective  hunger  contractions  and  the  subjective 
hunger  sensations. 

Depression  or  inhibition  of  hunger  by  smoking  is  rendered 
probable  by  the  fact  that,  at  least  in  man,  anything  which  stimu- 
lates the  sensory  nerve-endings  in  the  mouth  and  in  the  gastric 
mucosa  inhibits  the  gastric  hunger  contractions  in  direct  proportion 
to  the  intensity  of  the  stimulation.  Smoking  stimulates  the  nerve- 
ending  in  the  mouth  in  varying  degrees,  according  to  the  kind  of 
tobacco  used.  Smoking  frequently  involves  stimulation  of  the 
nerve-endings  in  the  gastric  mucosa  owing  to  the  swallowing  of 
saliva  containing  nicotine,  oils,  tannic  acid,  and  other  irritating 
substances.  Smoking  may  also  act  on  the  hunger  mechanism  in  a 
third  way,  that  is,  through  absorption  of  nicotine  and  other  products 
of  the  combustion.  The  third  possibility  has  not  been  investigated. 
It  is  well  established,  however,  that  even  small  quantities  of  nicotine 
in  the  blood  leads  to  nausea  and  vomiting.  Nausea  and  vomiting 
are  accompanied  by  atony  of  the  gastric  fundus,  which  insures 
absence  of  hunger  contractions  and  hunger  sensations. 

The  effects  of  smoking  on  the  gastric  hunger  contractions  were 
first  studied  on  Mr.  V.,  our  young  man  with  the  permanent  gastric 
fistula.    In  his  case  smoking  (cigars)  leads  invariably  to  inhibition 

199 


200        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

of  the  hunger  contractions.  But  Mr.  V.  is  not  a  habitual  smoker. 
It  is  therefore  possible  that  the  results  obtained  on  him  were  simply 
due  to  the  condition  of  nausea  or  disgust  that  smoking  usually 
produces  in  the  novice  and  hence  were  not  applicable  to  persons 
used  to  smoking. 

The  tests  were  repeated  on  several  habitual  smokers.  So  far 
as  smoking  influences  the  gastric  hunger  contractions  this  influence 
is  in  the  direction  of  inhibition.  This  inhibition  appears  to  depend 
on  the  intensity  of  stimulation  of  the  nerve-endings  in  the  mouth, 
a  cigarette  or  ''mild"  cigar  causing  only  slight  inhibition,  while  a 
"strong"  cigar  or  pipe  causes  complete  and  prolonged  inhibition, 
even  when  the  gastric  hunger  contractions  are  at  their  maximum. 

If  the  cigar  or  pipe  causes  very  strong  stimulation  of  the  nerve- 
endings  in  the  mouth,  the  inhibition  of  the  hunger  contractions 
may  continue  from  5  to  15  minutes  after  the  cessation  of  the 
stimulation.  Thus  even  a  brief  period  of  smoking  may  suppress 
an  entire  hunger  period. 

The  subjective  sensation  of  hunger  is  diminished  or  abolished 
parallel  with  the  gastric  hunger  contractions.  But  it  seems  to 
the  authors  that  even  a  ''mild"  smoke  diminished  the  sensation 
of  hunger  rather  more  than  one  might  infer  from  the  slight  depres- 
sion of  the  contractions.  This  is  probably  due  to  the  deviation  of 
attention,  the  smoking  acting  partly  as  a  "counter-irritant." 

Smoking  inhibits  the  gastric  hunger  contractions.  It  is  prac- 
tically certain,  even  in  the  absence  of  direct  experiments,  that 
moderate  smoking  does  not  inhibit  the  gastric  movements  of  diges- 
tion. The  reason  for  this  difference  in  the  action  of  the  same 
condition  on  the  empty  and  on  the  filled  stomach  is  not  clear. 

The  experiments  with  constriction  of  the  belt  were  made  on 
three  normal  men.  The  tests  were  made  with  the  subject  standing 
up,  sitting,  and  lying  on  the  back,  and  at  all  stages  of  the  gastric 
hunger  contractions. 

Strong  contraction  of  the  abdominal  belt  leads  nearly  always 
to  inhibition  of  the  gastric  hunger  contractions  of  weak  or  moderate 
strength,  lasting  from  5  to  15  minutes.    The  inhibition  may  be 


NERVOUS  CONTROL  OF  THE  HUNGER  MECHANISM      201 

partial  or  complete,  but  in  either  case  the  hunger  contractions 
reappear  despite  the  continued  pressure  of  the  belt.  This  inhibition 
is  obtained  even  when  the  belt  constriction  is  moderate,  so  that  no 
discomfort  or  pain  is  produced. 

When  the  gastric  hunger  contractions  are  strong  (the  middle 
of  a  hunger  period),  constriction  of  the  belt  never  causes  complete 
inhibition.  But  so  far  as  the  increased  abdominal  pressure  affects 
the  hunger  contractions,  the  influence  is  in  the  direction  of  inhibi- 
tion. The  individual  hunger  contractions  are  weakened  without 
suffering  much  change  in  the  rate.  Frequently,  however,  even  a 
belt  constriction  that  caused  considerable  discomfort  has  practically 
no  influence  on  the  hunger  contractions,  particularly  if  the  subject 
is  lying  down. 

When  the  gastric  hunger  contractions  are  at  their  maximum  in 
rate  and  amplitude,  as  is  ordinarily  the  case  near  the  end  of  a 
hunger  period,  no  amount  of  belt  constriction  seems  to  influence 
the  contractions.  When  this  stage  of  the  hunger  period  is  reached 
the  hunger  pangs  run  their  normal  course  in  the  presence  of  even 
painful  belt  pressure. 

All  three  subjects  agreed  that  the  belt  constriction  appeared 
to  diminish  or  interfere  with  the  hunger  sensation  to  a  greater 
extent  than  seemed  warranted  from  its  effect  on  the  hunger  con- 
tractions. Several  factors  are  probably  involved  in  this  discrepancy. 
(i)  The  belt  constriction  distracts  the  attention  from  the  hunger 
impulses  by  stimulation  of  nerve-endings  in  the  viscera,  especially 
those  of  the  peritoneum.  (2)  Strong  pressure  on  the  abdomen  from 
without  appears  to  induce,  temporarily,  a  condition  stimulating  in 
a  feeble  way  the  complex  sensation  of  satiety. 

According  to  R.  Lennhoff,^  hunger  and  appetite  are  appeased 
with  a  less  quantity  of  food  when  the  belt  is  constricted  than  when 
the  intra-abdominal  pressure  is  regulated  solely  by  the  tonus  of 
the  abdominal  muscles.  Lennhoff  ascribes  this  to  depression  of 
hunger  and  appetite  by  the  pressure  of  the  belt.  His  observation 
is  probably  correct,  but  his  explanation  is  erroneous.  In  a  normal 
person  the  actual  hunger  contractions  and  hunger  sensations  are 

^Quoted  in  Jour.  Amer.  Med.  Assoc. ^  LX  (1913),  41. 


202        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

stopped  by  the  first  few  morsels  of  food  swallowed,  while  this  may 
actually  increase  the  appetite  through  stimulation  of  nerve-endings 
in  the  mouth  and  in  the  mucous  membrane  of  the  esophagus  and 
stomach.  This  appetite  sensation  is  gradually  counteracted  by 
the  sensation  complex  of  satiety,  which  depends  in  part  on  the 
distension  of  the  stomach  with  corresponding  readjustment  of  the 
tonus  of  the  abdominal  muscles.  This  feeling  of  fulness,  which 
appears  to  be  referred  to  the  abdomen  as  a  whole,  is  probably 
developed  with  less  intake  of  food  when  the  abdominal  wall  is 
mechanically  prevented  from  relaxing  owing  to  the  pressure  of 
the  belt. 

We  have  practically  nothing  but  conjectures  to  offer  in  way  of 
explanation  of  the  mechanisms  involved  in  these  inhibitions  of  the 
gastric  hunger  contractions  by  strong  pressure  on  the  abdomen. 
Strong  pressure  on  the  abdomen  causes  temporary  inhibition  of 
the  gastric  hunger  contractions  in  dogs,  but  the  manipulation 
greatly  disturbs  them,  and  disturbance  from  any  cause  leads  to  a 
temporary  inhibition  of  the  empty  stomach  in  dogs  with  the 
splanchnic  nerves  intact.  In  dogs  with  the  splanchnic  nerves  Sec- 
tioned on  both  sides  strong  pressure  on  the  abdomen  causes  no 
distinct  inhibition  of  the  gastric  hunger  contractions.  This  points 
to  the  conclusion  that  belt  constriction  causes  gastric  inhibition, 
not  by  direct  pressure  on  the  stomach,  but  by  direct  stimula- 
tion of  inhibitory  nerves,  or  by  mechanical  (or  sympathetic) 
stimulation  of  the  adrenal  glands,  and  through  long  reflexes.  Belt 
constriction  involves  stimulation  of  cutaneous  nerve-endings,  but 
a  gentle  stimulation  of  the  tactile  nerve-endings  in  the  skin  alone 
does  not  lead  to  this  inhibition.  The  afferent  path  of  the  reflex 
must  therefore  involve  abdominal  proprioceptors.  The  splanchnic 
nerves  probably  constitute  the.  efferent  path  of  the  reflex.  We 
do  not  wish  to  be  understood  as  denying  the  existence  of  local 
inhibitory  mechanisms  that  may  be  stimulated  by  mechanical 
manipulation  of  the  abdominal  organs,  but  our  results  indicate 
that  strong  belt  constriction  is  not  a  sufficient  stimulus  for  such 
local  mechanisms. 


NERVOUS  CONTROL  OF  THE  HUNGER  MECHANISM      203 

II.      INFLUENCE   OF  PHYSICAL  EXERCISE  AND  EXTERNAL   COLD 
ON  THE  HUNGER  MECHANISM 

So  far  we  have  been  unable  to  initiate  or  augment  the  gastric 
hunger  contractions  in  man  or  experimental  animals  by  any  sensory 
stimulation  or  central  nervous  processes.  We  have  seen  that  so  far 
as  these  nervous  processes  affect  hunger  it  is  in  the  direction  of 
inhibition.  It  is  singular,  indeed,  that  the  inhibitory  mechanisms 
are  so.  readily  called  into  play,  while  motor  reflexes  are  either 
inaccessible  or  lacking,  especially  since  the  utility  of  some  of  the 
inhibitory  reflexes  are  open  to  question  at  present. 

From  the  point  of  view  of  biological  adaptation  we  might  expect 
the  vagogastric  tonus  to  be  directly  affected  by  voluntary  muscular 
activity  and  by  exposure  to  cold,  since  both  conditions  involve 
increased  oxidation  and  consequently  increased  need  of  food. 

Muscular  activity  may  augment  the  gastric  hunger  activity  by 
increasing  the  vagus  tonus  as  well  as  by  chemical  changes  in  the 
blood.  The  same  applies  to  stimulation  of  the  cold  nerve-endings 
of  the  skin.  However,  it  is  probable  that  if  these  conditions  cause 
increase  in  the  vagus  tonus  reflexly,  this  response  is  more  prompt 
than  that  induced  by  the  changes  in  the  blood  following  the  increase 
or  decrease  in  body  metabolism  due  to  stimulation.  It  is  generally 
recognized  that  exercise,  cold  climate,  and  cold  baths  increase 
appetite  and  hunger.  It  does  not  follow  that  these  conditions 
actually  augment  the  gastric  hunger  contractions.  The  increase 
in  hunger  and  appetite  may  be  only  apparent,  that  is,  may  reflect 
a  condition  of  increased  excitability  of  parts  of  the  central  nervous 
system,  so  that  the  afferent  impulses  that  give  rise  to  the  sensation 
of  hunger  and  appetite  produce  a  greater  central  effect.  •  If  the 
gastric  hunger  contractions  are  actually  increased,  this  may  be 
due  to  changes  in  the  blood  rather  than  to  increased  vagus  tonus. 

It  is  well  known  that  exposure  of  the  skin  to  cold  (as  by  bathing 
in  ice  water)  may  induce  contracture  or  ''cramps"  of  the  digestive 
tract.  This  is  especially  the  case  during  the  height  of  gastric  and 
intestinal  digestion.  These  cramps  and  contractures  may  be  the 
result  of  circulatory  disturbances  or  of  changes  in  the  blood  rather 
than  a  direct  reflex  effect.    Central  processes  are  also  able  to  induce 


204        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

contraction  of  the  large  intestine  and  the  rectum,  as  shown  by 
involuntary  defecation  in  cases  of  great  anxiety  or  fear. 

I.      EXPERIMENTAL  PROCEDURE 

1.  Dogs. — Dogs  with  simple  gastric  fistulas  were  trained  to  run 
in  a  treadmill.  When  trained  to  run  without  urging  or  interference, 
records  were  taken  of  the  contractions  of  the  empty  stomach  so  as 
to  determine  (i)  whether  muscular  activity  induces  hunger  con- 
tractions in  the  quiescent  stomach,  and  (2)  whether  muscular 
activity  augments  the  hunger  contractions  of  an  active  stomach. 

The  hunger  contractions  of  the  stomach  of  dogs  were  recorded 
for  2  to  4  hours  after  a  day's  fast,  the  dogs  being  taken  direct  from 
the  kennel  without  being  exercised.  On  other  days  the  same  dogs 
were  taken  out  for  a  4-  to  6-mile  brisk  walk  before  the  2-  to  4-hour 
recording  period. 

Records  of  the  gastric  hunger  contractions  were  taken  with  the 
dog  lying  quietly  in  the  lap  of  an  assistant.  Then  the  body  of  the 
animal  was  surrounded  with  an  ice  pack,  or  the  dog  placed  directly 
on  a  slab  of  ice.  After  some  training  the  dogs  do  not  appear  much 
disturbed  by  the  ice  pack  or  slab  of  ice.  The  ice  pack  was  applied 
with  the  stomach  quiescent  as  well  as  in  hunger  activity. 

All  of  these  procedures  were  used  on  normal  dogs  and  on  dogs 
with  the  splanchnic  nerves  sectioned  on  both  sides,  in  order  to  have 
the  tonus  fibers  of  the  vagi  unopposed  by  the  splanchnic  inhibitory 
influence. 

2.  Man. — The  tests  were  made  on  the  author,  on  Mr.  V.  (the 
gastric  fistula  case),  and  on  three  assistants  (J.  H.  L.,  S.  J.  O., 
A.  M.  P.). 

Records  were  taken  of  the  gastric  hunger  and  tonus  contraction 
with  the  man  standing  or  walking  or  running  in  situ.  Tests  were  also 
made  after  muscular  exercise  (playing  tennis,  walking  6  to  12  miles). 

The  influence  of  exposure  of  the  body  to  cold  on  the  gastric 
hunger  mechanism  was  tested  in  the  following  way:  (i)  While 
records  of  the  gastric  tonus  and  hunger  contractions  were  being 
taken,  the  man,  stripped  of  his  clothes,  was  subjected  to  cold  or 
warm  showers  for  varying  periods,    The  cold  showers  were  at  times 


NERVOUS  CONTROL  OF  THE  HUNGER  MECHANISM      205 

sufficiently  cold  or  prolonged  to  cause  intense  shivering.  (2)  The 
man,  stripped  of  his  clothes  in  a  cold  room,  was  covered  up  on  a 
couch  so  as  to  feel  comfortably  warm.  At  the  desired  moment  in 
the  gastric  activity,  that  is,  during  a  period  of  quiescence  or  in  the 
midst  of  a  period  of  hunger  contractions,  the  covers  were  removed 
and  the  cold  air  of  the  room  set  in  motion  by  a  fan  placed  close  to 
the  person.  This  brought  on  shivering  in  a  few  minutes.  (3)  The 
man  arose  at  7:00  a.m.  and,  without  the  usual  cold  bath  and 
breakfast,  proceeded  to  the  laboratory,  and  records  of  the  gastric 
tonus  and  hunger  contractions  were  taken  from  8 :  00  a.m.  to  1 2 :  00  M. 
These  served  as  controls.  On  the  other  days  the  man  arose  at  6 :  00 
A.M.,  took  a  cold  bath  (this  was  prolonged  until  the  discomfort 
became  very  severe),  followed  by  a  brisk  walk,  when  records  were 
taken  from  8:00  a.m.  to  12:00  M. 

2.      RESULTS   ON  DOGS 

I.  Effects  of  running  in  treadmill. — The  initial  effect  on  gastric 
tonus  and  hunger  contractions  of  running  in  the  mill  is  always  in 
the  direction  of  inhibition — usually  complete  inhibition — and  if  the 
dog  is  started  running  in  the  midst  of  a  period  of  gastric  quiescence 
there  is  no  evidence  of  increased  gastric  tonus  or  beginning  of 
hunger  contractions.  If  the  dog  is  made  to  run  at  high  speed  the 
inhibition  persists  during  the  entire  period,  even  if  the  running  is 
kept  up  for  one  or  two  hours.  When  the  dogs  ran  at  rather  high 
speed  for  an  hour  or  more  the  gastric  inhibition  usually  persisted 
from  20  to  40  minutes  after  the  dog  stopped  running.  The  return 
of  gastric  tonus  and  hunger  contractions  in  such  cases  is  very 
gradual.  But  frequently  when  the  gastric  tonus  finally  recovered 
after  a  running  period  it  was  higher  than  before  the  dogs  began 
to  run.  Thus  a  dog  showing  type  I  or  II  of  hunger  contractions 
when  he  started  to  run  in  the  mill  showed  an  increased  tonus  and 
type  III  of  hunger  contractions  30  minutes  after  he  stopped  running, 
while  the  running  period  itself  was  accompanied  by  complete  gastric 
inhibition.  If  the  dog  runs  only  moderately  fast  in  the  mill  the 
gastric  tonus  and  hunger  contractions  reappear  during  the  running 


2o6       CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

period,  or  come  on  during  the  running,  in  case  the  dog  is  started 
when  the  empty  stomach  is  quiescent. 

These  facts  indicate  that  the  carnivorous  animal  in  pursuit  of 
its  prey  must  be  urged  on  by  something  else  than  the  pangs  of 
hunger,  as  these  are  inhibited  by  the  chase.  Brisk  walking  or 
running  leads  also  to  inhibition  of  the  digestion  movements  of  the 
stomach,  according  to  the  observations  of  Cohn  on  dogs.  Bender  on 
man,  and  Scheunert  on  the  horse. 

2.  Effects  of  4-  to  6-mile  walk. — Eight  tests  (with  a  corresponding 
number  of  controls)  on  two  dogs  failed  to  show  any  marked  effect 
of  a  4-  to  6-mile  walk  on  the  gastric  hunger  contractions  either  in 
the  way  of  increase  or  decrease,  the  records  being  taken  during  the 
two  hours  following  the  walk.  These  walks  certainly  caused  no 
depression  of  the  dog's  hunger  contractions.  But  the  dog  that 
showed  type  II  contractions  in  the  control  usually  showed  type  II 
contractions  after  the  walk,  with  no  definite  increase  either  in  rate 
or  intensity.  This  should  be  noted,  however,  that  after  these  walks 
both  dogs  showed  greater  restlessness  than  when  taken  from  the 
kennels  directly  to  the  laboratory.  They  were  not  so  easily  quieted 
in  the  lap  of  the  assistant.  This  rather  restless  condition  of  the 
dogs  may  have  counteracted  any  augmentation  of  gastric  hunger 
contractions  due  to  the  walk,  as  restlessness  from  any  cause  tends 
in  the  dog  to  inhibit  the  hunger  contractions. 

3.  Effect  of  intense  stimulation  of  the  cutaneous  nerve-endings  for 
the  sensation  of  cold. — When  a  dog  is  lying  quietly  and  comfortably 
in  the  lap  of  an  assistant,  surrounding  the  dog  with  an  ice  pack  or 
placing  him  directly  on  a  slab  of  ice  leads  to  struggling  and  rest- 
lessness. After  a  number  of  repetitions  of  these  procedures  most 
dogs  become  so  accustomed  to  it  that  they  pay  little  or  no  attention 
to  the  change  and  show  no  restlessness  or  struggling.  If  the  dog 
is  disturbed  or  struggles  when  placed  on  the  slab  of  ice  or  surrounded 
by  an  ice  pack  there  always  follows  a  temporary  inhibition  of 
gastric  tonus  and  hunger  contractions.  But  this  does  not  indicate 
the  initial  or  primary  effect  of  stimulation  of  the  cutaneous  nerve- 
endings  for  cold,  because  the  same  type  of  inhibition  is  induced  by 
restlessness  or  struggle  for  any  cause.    After  the  dog  is  trained  to 


NERVOUS  CONTROL  OF  THE  HUNGER  MECHANISM      207 

these  procedures  strong  stimulation  of  the  cutaneous  nerve-endings 
for  cold  by  the  ice  pack,  by  placing  the  dog  on  a  slab  of  ice,  or  by 
turning  on  an  electric  fan  in  a  cold  room  after  uncovering  the  dog, 
has  no  immediate  effect  on  the  gastric  tonus  and  hunger  contrac- 
tions. There  is  usually  an  increase  in  the  intra-abdominal  pressure 
owing  to  the  increased  tonus  of  the  abdominal  muscles.  If  the  ice 
pack  is  applied  during  a  period  of  gastric  quiescence  there  is  no 
immediate  increase  in  gastric  tonus  or  initiation  of  the  hunger 
contractions,  even  though  the  dog  starts  to  shiver  violently  in  a 
few  minutes.  If  the  ice  pack  is  applied  during  the  hunger  contrac- 
tions, these  contractions  do  not  change  appreciably  either  in  rate 
or  strength,  at  least  for  some  time.  This  is  true  even  when  the  dog 
shivers  considerably.  It  would  thus  seem  that  the  vagus  centers 
governing  the  gastric  tonus  are  not  directly  affected  by  even  very 
strong  stimulation  of  the  cutaneous  nerve-endings  for  cold. 

In  several  instances  the  continued  application  of  the  ice  pack 
(30  to  40  minutes),  and  in  consequence  continued  shivering,  led  to  a 
gradually  increased  gastric  tonus  and  the  appearance  of  type  III 
hunger  contractions.  These  may  be  due  to  changes  in  the  blood 
as  a  result  of  increased  oxidation,  or  they  may  appear  from  causes 
not  connected  with  the  stimulation  of  the  cold  nerve-endings. 
Such  change  in  the  hunger  contractions  is  not  infrequent  in  dogs, 
even  when  they  are  lying  undisturbed  and  comfortable  in  the  lap 
of  an  assistant. 

It  is  conceivable  that  the  stimulation  of  the  cold  nerve-endings 
in  the  skin  does  influence  the  vagogastric  tonus  centers,  but  the 
stimulation  acts  equally  on  the  gastric  inhibitory  mechanism  via 
the  splanchnic  nerves,  so  that  the  net  result  on  the  empty  stomach 
is  nil.  This  possibility  is  cleared  up  by  the  test  on  dogs  with  section 
of  both  splanchnic  nerves.  Tests  were  made  on  two  dogs  on  which 
the  operation  had  been  performed.  The  results  were  practically 
identical  with  those  on  normal  dogs.  The  ice  pack  neither  decreased 
nor  increased  the  gastric  hunger  contractions.  It  is  therefore  clear 
that  the  nervous  impulses  that  give  rise  to  the  sensation  of  cold  and 
induce  increased  neuromuscular  tonus  in  general  have  no  direct 
action  on  the  vagogastric  tonus  centers. 


2o8        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 


■1 1  f 

''fdl0j0lll^i 

Fig.  25 


NERVOUS  CONTROL  OF  THE  HUNGER  MECHANISM      209 


Fig.  :25. — A,  tracing  from  the  empty  stomach  of  a  dog.  I.  Dog  standing  in 
treadmill,  stomach  showing  type  I  hunger  contractions.  At  x,  the  dog  begins  to  run 
in  the  mill  with  the  result  that  gastric  hunger  contractions  are  promptly  inhibited. 
The  running  was  kept  up  for  60  minutes.  II.  Record  from  stomach  of  same  dog  45 
minutes  after  he  ceased  running,  showing  increased  gastric  tonus.  B,  tracing  from 
the  empty  stomach  of  man  (A.  J.  C.)  in  standing  position;  beginning  of  a  hunger  period. 
At  X,  the  man  began  running,  with  the  result  that  the  hunger  contractions  were 
promptly  inhibited.  C,  tracing  from  the  empty  stomach  of  dog  with  section  of  splanch- 
nic nerves  on  both  sides.  At  x  the  dog  is  surrounded  by  an  ice  pack.  D,  tracing  from 
the  empty  stomach  of  man  (A.  J.  C.)  in  the  midst  of  a  period  of  hunger  contractions. 
The  man  was  stripped  and  covered  up  with  blankets  in  a  cold  room  (20°  C).  At  x 
the  covers  were  removed  and  a  fan  close  to  the  man  started.  Shivering  began  at  x'; 
showing  a  temporary  but  partial  inhibition  of  the  hunger  contractions.  E,  records 
of  culminations  of  periods  of  gastric  hunger  contractions  of  A.  J.  C.  I.  The  ordinary 
type  of  ending  of  the  hunger  periods  without  tetanus.  II.  Hunger  period  ending  in 
incomplete  tetanus  three  hours  after  intense  stimulation  of  the  cold  nerve-endings 
(bath  at  10°  C.  for  15  minutes). 


210        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

3.      RESULTS   ON   MAN 

1.  Direct  ejfect  of  muscular  exercise. — Standing  or  walking  in  situ 
has  no  effect  on  the  gastric  tonus  or  the  hunger  contractions.  But 
running  in  situ  promptly  inhibits  the  hunger  contractions.  The 
degree  and  duration  of  the  inhibition  are  on  the  whole  directly  pro- 
portional to  the  speed  of  the  running.  In  some  cases  walking  seemed 
to  prolong  a  hunger  period  without  changing  the  rate  or  intensity 
of  the  individual  contractions.  In  no  case  did  walking  or  running 
induce  hunger  contractions  in  the  quiescent  stomach.  The  results 
on  man  are  thus  identical  with  the  results  on  dogs.  In  both  species 
rapid  running  is  accompanied  by  inhibition  of  the  gastric  tonus 
and  hunger  contractions.  In  the  case  of  the  dog  running  in  the 
treadmill,  one  cannot  be  sure  that  the  exercise  is  strictly  voluntary 
and  enjoyable.  The  inhibition  may  therefore  be  due  to  certain 
emotional  states  (anxiety,  discomfort,  mild  anger,  or  fear).  This 
possibility  is  eliminated  by  the  tests  on  man.  In  the  men  the 
conditions  of  the  emotions  when  running  in  place  were  not  different 
from  that  when  standing  or  walking  in  place.  In  no  case  was  the 
running  carried  to  the  point  of  respiratory,  cardiac,  or  muscular 
distress. 

2.  After-effects  of  muscular  exercise. — Moderate  exercise  in  the 
form  of  playing  tennis  or  walking  4  to  8  miles  was  taken  in  the  after- 
noon. No  supper  was  taken,  and  the  motor  condition  of  the 
empty  stomach  was  recorded  from  8:00  p.m.  to  12:00  midnight. 
The  tracings  obtained  on  the  days  specific  exercise  was  taken 
show  on  the  whole  greater  gastric  hunger  activity  than  the  controls. 
The  periods  of  quiescence  become  shorter.  This  tends  to  make  the 
gastric  hunger  contractions  more  or  less  continuous,  and  there 
appears  to  be  some  increase  in  the  rate  of  the  contractions.  A 
typical  experiment  (S.  J.  O.)  may  be  cited  in  the  way  of  illustration. 

Record  of  control  day. — ^Lunch  1 130  p.m.  No  special  exercise.  No  supper. 
Period  of  observation  8:00  p.m  to  12  midnight. 

8 :  00  to  10 :  00  P.M.     Stomach  practically  quiescent. 
10:00  to  10:40.  Strong  hunger  contractions,  ending  in  tetanus. 

I o :  40  to  11:35.  Stomach  quiescent . 

11:35  to  12:05.  Moderate  hunger  contractions  ending  in  tetanus. 


NERVOUS  CONTROL  OF  THE  HUNGER  MECHANISM       211 

Record  oj  exercise  day. — Lunch  1:30  p.m.  No  supper.  Tennis  4:00  to 
5:00  P.M.;  walking  6:00  to  7:00  p.m.  Period  of  observation  8:00  p.m.  to  12 
midnight. 

8 : 1 5  to    9 :  50  p.m.     Practically  continuous  hunger  contraction  ending 

in  strong  tetanus. 
9:50  to  10:20.  Stomach  quiescent. 

10: 20  to  II :4o.  Strong  hunger  contractions  ending  in  tetanus. 

(Control  day,  70  minutes;  exercise  day,  190  min- 
utes.) Total  duration  of  hunger  periods  from 
8:00  P.M.  to  12  midnight. 

In  some  instances  there  was  no  marked  difference  between 
records  of  the  control  and  the  exercise  days.  This  is  to  be  expected, 
since  the  activity  of  the  gastric  hunger  mechanism  depends  in  part 
on  factors  not  understood  or  controlled.  Exercise  that  brings  on  a 
degree  of  fatigue  bordering  on  exhaustion  seems  to  depress  the 
gastric  hunger  mechanism.  But  our  experiments  on  this  point  are 
as  yet  too  few  to  permit  a  final  conclusion. 

3 .  Direct  effect  of  stimulation  of  the  cold  nerve-endings  of  the  skin. — 
The  immediate  effect  of  stimulation  of  the  cold  nerve-endings  of 
the  skin  by  ice  pack,  alcohol  bath,  cold  shower  bath,  or  cooled  air 
is  inhibition  of  the  gastric  tonus  and  hunger  contractions,  and  the 
degree  of  inhibition  is  proportional  to  the  intensity  of  the  stimula- 
tion. In  no  instance  did  we  observe  an  initial  increase  in  gastric 
tonus  and  hunger  contractions.  When  the  stimulation  is  continued 
the  inhibitory  effects  gradually  diminish,  even  though  the  man 
shivers  intensely  from  the  cold.  In  this  way  the  gastric  hunger 
contractions  may  return  to  their  normal  rate,  intensity,  and  regu- 
larity, while  the  man  is  shivering  and  jerking  like  a  dog  in  mild 
parathyroid  tetany.  It  may  be  noted  in  this  connection  that  mild 
and  in  some  instances  fairly  severe  parathyroid  tetany  in  dogs  does 
not  appreciably  influence  the  gastric  hunger  contractions. 

Intense  stimulation  of  the  heat  nerve-endings  of  the  skin  (hot 
shower)  produces  practically  the  same  initial  inhibition  as  the 
corresponding  stimulation  of  the  cold  nerve-endmgs. 

While  it  is  true  that  on  prolonged  stimulation  of  the  cold  nerve- 
endings  of  the  skin,  during  a  period  of  gastric  hunger  contractions, 
the  inhibitory  effects  gradually  disappear,  so  that  the  contractions 


212        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

reappear  in  their  nonnal  intensity,  these  contractions  are  always 
felt  as  weaker  than  the  nonnal,  or  may  not  be  felt  at  all.  Evidently 
the  intense  sensation  of  cold  dominates  consciousness  to  the  exclu- 
sion of  the  gastric  hunger  pangs. 

It  is  well  known  that  strong  stimulation  of  the  cold  nerve- 
endings  of  the  skin  causes  a  reflex  increase  of  tonus  of  the  urinary 
bladder.  In  several  instances  we  started  these  stomach  tests  on  the 
men  at  a  time  when  their  bladders  were  known  to  contain  50  to 
200  c.c.  of  urine.  This  permitted  us  to  compare  the  reflex  effect 
of  cold  on  the  stomach  and  bladder  tonus  without  a  balloon  in  the 
bladder.  When  the  cold  stimulation  began  during  a  period  of 
gastric  quiescence  and  was  continued  long  enough  to  induce  intense 
shivering,  a  strong  desire  to  micturate  soon  developed  while  there 
was  no  evidence  of  increased  gastric  tonus.  Prolonged  cold  stimu- 
lation may  produce  so  great  a  tonus  of  the  bladder  that  micturition 
cannot  be  inhibited  voluntarily.  The  tonus  centers  of  the  urinary 
bladder  are,  the  vagogastric  tonus  centers  are  not,  directly  in- 
fluenced by  cold  stimulation  of  the  skin. 

When  the  cold  nerve-endings  of  the  skin  are  stimulated,  as 
described  above,  during  a  period  of  quiescence  of  the  empty  stom- 
ach, the  stomach  remains  quiescent.  If  there  is  any  change  in  the 
gastric  tonus  it  is  in  the  direction  of  inhibition.  Nevertheless,  this 
cold  stimulation,  if  not  sufficiently  intense  to  be  painful,  seemed  to 
induce  a  ^'sensation  of  emptiness"  in  the  abdominal  region,  a 
sensation  that  seemed  to  be  associated  with  appetite  and  desire 
for  food.  We  record  this  with  some  hesitation,  for  this  sensation 
of  emptiness  may  be  purely  subjective  (auto-suggestion) .  It  may 
also  be  due  to  the  increased  tonus  of  the  abdominal  muscles.  In 
any  event  this  sensation  is  clearly  different  from  the  hunger  pangs. 

4.  After-effect  of  the  stimulation  of  the  cold  nerve-endings  of  the 
skin. — All  of  the  tests  in  this  group  were  made  on  one  man  (A.  J.  C). 
A  prolonged  cold  bath,  from  6:00  to  7  :oo  a.m.,  followed  by  a  brisk 
walk,  nearly  always  resulted  in  increased  hunger  activity  of  the 
stomach  as  recorded  for  the  period  8:00  a.m.  to  12:00  M.  The 
temperature  of  the  water  varied  from  5°  C.  to  15°  C.  The  subject 
remained  in  the  water  as  long  as  was  deemed  safe  (10  to  20  minutes) 
despite  discomfort  and  pain.    Water  at  this  temperature  soon  brings 


NERVOUS  CONTROL  OF  THE  HUNGER  MECHANISM      213 

on  shivering,  contracture,  and  at  times  severe  headache,  and  it 
requires  much  vigorous  exercise  to  restore  the  feeling  of  warmth. 
Rubbing  the  skin  (rough  towel)  seems  to  be  of  little  avail.  A 
typical  experiment  may  be  cited  in  illustration. 

Control  record. — ^No  bath  or  breakfast.  Observation  period  8:00  a.m.  to 
12:00  M. 

8:50  to  10:00  A.M.     26  fairly  strong  hunger  contractions;  no  tetanus. 
ii:ootoii:45.  22  fairly  strong  hunger  contractions;  no  tetanus. 

Gastric  tonus  on  the  average  5  cm.  bromoform. 
Test  period. — 6:00  to  6:15  a.m.,  cold  bath  (temperature  of  water  10°  C). 
No  breakfast.    Observation  period  8:00  a.m.  to  12:00  m. 

8:00  to    9:00  a.m.    32  strong  contractions;  no  tetanus. 
9:45  to  10:25.  23  fairly  strong  contractions;   no  tetanus. 

II :  15  to  II  :45.  19  strong  contractions  ending  in  tetanus. 

Gastric  tonus  on  the  average  8  cm.  bromoform. 
Control  period. — ^48  hunger  pangs;  no  tetanus. 
Test  period. — 74  hunger  pangs;  tetanus. 

Under  ordinary  conditions  the  periods  of  gastric  hunger  con- 
tractions of  the  author  do  not  end  in  tetanus,  but  the  hunger  tetanus 
appears  after  3  to  4  days'  complete  starvation.  Intense  stimulation 
of  the  cold  nerve-endings  for  15  to  30  minutes  thus  seems  to  bring 
about  a  condition  similar  to  prolonged  starvation.  This  is  in  har- 
mony with  the  observation  of  Lusk  that  such  stimulation  quickly 
renders  the  liver  free  from  glycogen.  This  effect  of  cold  on  the 
gastric  hunger  mechanism  is  obviously  an  indirect  one,  or  brought 
about  through  changes  in  the  blood,  and  is  not  a  direct  reflex  from 
the  skin. 

Lusk  has  shown  that  intense  cold  leads  to  quicker  and  more 
complete  oxidation  of  the  body  glycogen  than  prolonged  starvation. 
And  it  is  interesting  to  note  that  the  same  stimulus  causes  not  only 
an  increase  in  the  gastric  hunger  contractions,  but  also  an  even 
greater  increase  in  the  subjective  hunger  and  appetite  sensations, 
probably  owing  to  an  increased  excitability  of  the  central  nervous 
system.  The  increased  desire  to  eat  after  a  cold  bath,  in  the  case 
of  the  healthy  individual,  is  a  universal  experience.  I  have  inves- 
tigated this  matter  in  the  case  of  young  children,  with  whom  habit 
or  intelligence  cannot  be  assigned  as  the  cause  for  seeking  food 


214        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

after  a  cold  bath.    It  was  found  that  young  children  react  in  the 
same  way  as  adults. 

While  these  observations  include  only  two  species  (man,  dog), 
it  does  not  seem  likely  that  the  gastric  vagotonus  mechanism  will 
have  different  reflex  associations  in  other  animals.  But  this  opinion 
should  not  stand  in  the  way  of  actual  investigation  of  the  condition 
in  other  vertebrates  as  well  as  in  the  invertebrates.  In  man  and  in 
dogs  the  situation  appears  to  be  this:  The  vagus  motor  nuclei 
in  the  medulla  control,  in  part,  the  tonus  and  hunger  contractions 
of  the  stomach.  The  tonus  of  the  vagus  nuclei,  in  turn,  are  con- 
trolled by  the  condition  of  the  blood  rather  than  by  afferent  nervous 
impulses,  unless  sensory  impulses  from  the  stomach  musculature 
itself  play  such  a  role.    This  possibihty  is  now  under  investigation. 

iii.    afferent  or  sensory  paths  of  the  hunger  complex 

and  the  question  of  the  cerebral 

''hunger  center" 

1.  Role  of  the  vagi. — The  vagi  nerves  are  the  main,  if  not  the 
only,  afferent  pathway  for  the  gastric  hunger  impulses,  although 
Luciani  assumes  that  some  of  the  hunger  impulses  from  the 
stomach  are  carried  by  the  sympathetic  (splanchnic)  fibers.  If 
the  contraction  of  the  small  intestine  contributes  to  the  hunger 
sensation,  the  afferent  hunger  impulses  may  involve  sympathetic 
and  spinal  nerves,  but  all  sensory  conduction  from  the  stomach 
appears  to  be  confined  to  the  vagi,  because  no  central  reflexes  of 
any  kind  can  be  evoked  by  stimulation  of  the  stomach  after  section 
of  all  the  vagi  fibers  to  that  organ  (Miller) .  We  need  not  here  refer 
to  the  physiologists  who  have  argued  against  the  vagi  nerves  (and 
in  favor  of  the  splanchnics)  as  being  concerned  in  hunger  on  the 
basis  that  animals  will  continue  to  eat  after  section  of  these  nerves 
or  after  excision  of  the  stomach,  as  these  objections  have  already 
been  considered  and  refuted. 

2.  The  primary  hunger  center  is  therefore  the  sensory  nuclei  of 
the  vagi  nerves  in  the  medulla  (fasciculus  solitarius).  Some  of 
the  more  direct  hunger  reflexes  (such  as  salivation,  vasomotor 
fluctuations,  etc.)  may  be  carried  out  via  these  medullary  centers 
alone.     Luciani  assumes  also  spinal  hunger  centers  analogous  to 


NERVOUS  CONTROL  OF  THE  HUNGER  MECHANISM      215 

these  sensory  vagi  nuclei.  There  is  no  evidence  that  the  processes 
of  conscious  hunger  sensation  can  take  place  in  the  medullary 
nuclei. 

3'.  Role  of  the  optic  thalami  and  the  mid-brain. — The  important 
facts  in  this  connection  are  the  hunger  behavior  of  decerebrated 
animals  (acephalic  infants,  dogs,  pigeons,  frogs).  This  hunger 
behavior  has  already  been  ascribed.  These  animals  minus  the 
cerebral  hemisphere,  but  with  the  thalamic  region  of  the  brain 
intact,  exhibit  practically  all  the  hunger  behavior  of  normal  animals, 
except  the  intelligent  search  for  and  ingestion  of  the  food.  But 
even  this  statement  requires  limitation,  for,  according  to  Ewald,^ 
decerebrated  pigeons  and  frogs  will  finally  eat  spontaneously  if 
kept  in  good  condition  for  a  sufficient  time  (months)  after  the 
operation. 

Rogers  has  recently  made  the  important  observation  that  the 
hunger  behavior  of  the  decerebrated  pigeon  is  completely  abolished 
on  removal  of  the  optic  thalami.  It  is  thus  clear  that  this  region 
contains  important  nuclei  for  the  elaboration  of  the  bodily  responses 
to  the  hunger  impulses  from  the  stomach.  Whether  or  not  the 
processes  of  conscious  hunger  sensations  are  elaborated  in  the 
thalamus  cannot  be  determined  on  experimental  animals.  L.  R. 
Miiller  assumes  that  conscious  hunger  sensations  are  evoked  in  the 
mid-brain.  We  have  seen  that  hunger  is  essentially  pain,  and  some 
neurologists  take  the  position  that  the  sensation  of  pain  is  a  thala- 
mic rather  than  a  cortical  function.  This  view  is  supported  by  the 
extensive  studies  of  Head  and  Holmes  on  the  change  in  the  pain 
sense  in  persons  with  thalamic  lesions  and  intact  cortex.  The 
frequent  occurrence  of  excessive  hunger  or  polyphagia  in  persons 
with  tumors  of  the  pineal  glands  have  by  some  (Schiiller)  been 
interpreted  as  due  to  a  pressure  stimulation  of  subcortical  hunger 
centers.  Whether  the  thalamic  processes  caused  by  the  gastric 
hunger  contractions  are  conscious  or  merely  subconscious  reflexes, 
or  whether  the  nuclei  concerned  with  these  processes  are  identical 
with  those  involved  in  pain  sensation,  it  is  clear  that  the  thalamus 

^  Quoted  from  A.  L.  Gillespie,  The  Natural  History  of  Digestion,  New  York,  1898, 
286. 


2i6        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 


is  a  very  important  reflex  and  relay  station    for    the    afferent 
hunger  impulses. 

4.  Cortical  hunger  centers. — Concerning  these  practically  nothing 
is   known.      There    can   be   little   doubt   that   conscious   hunger 

involves  in  some  way  cortical 
processes,  and  one  might  expect 
the  part  of  the  cortex  involved 
would  be  contiguous  with  that 
for  the  gustatory  sense,  the  latter 
being  placed  in  the  hipochampal 
gyrus  by  the  majority  of  neurol- 
ogists and  psychiatrists.  Roux 
assumes  that  the  cortical  hunger 
center  is  in  the  Rolandic  area, 
thus  supporting  Bechterew,  who 
locates  the  conscious  taste  pro- 
cesses in  the  region  of  the  Rolandic 
area  which  innervates  the  muscles 
of  mastication  and  deglutition. 

To  recapitulate:  In  the  affer- 
ent phase  of  the  hunger  complex 
the  facts  clearly  established  are 
the  role  of  the  vagi,  and  the 
sensory  vagi  nuclei  in  the  medulla, 
and  the  great  importance  of  the 
thalamus.  The  cortical  factors  in 
hunger  are  unknown,  and  the  same 
applies  to  the  detailed  roles  of  the 
subcortical  hunger  centers  both 
in  health  and  in  disease.  This 
field  of  the  physiology  of  hunger 
is  therefore  mainly  ^'gaps  and 
guesses . "  It  remains  for  the  clini- 
cal investigator  to  correct  the  guesses  and  fill  up  the  gaps,  as  very 
little  can  be  done  with  these  problems  on  animals  below  man,  at 
least  with  the  methods  so  far  available  to  the  physiologist. 


Fig.  26. — Diagram  of  the  nervous 
mechanism  of  the  hunger  sense.  A ,  cer- 
ebrum. B,  optic  thalami.  C,  motor 
nuclei  of  the  vagi  nerves.  D,  sensory 
nuclei  of  the  vagi  nerves.  F,  medulla 
oblongata.  G,  spinal  cord.  H,  stomach. 
/,  visceral  sympathetic  ganglia.  K, 
splanchnic  nerves.  L,  motor  fibers  to 
the  stomach.  M,  sensory  paths  (hunger) 
to  cerebrum  (hypothetical).  N,  sensory 
fibers  from  stomach  in  the  vagi,  -|- 
indicates  motor,  —  indicates  inhibitory 
effects,  ->  indicates  direction  of  nerv- 
ous conduction. 


CHAPTER  XIII 

THE  CHEMICAL  CONTROL  OF  THE  HUNGER  MECHANISM 

I.      ANALYSIS   OF   THE  PROBLEM 

The  reader  will  recall  from  the  review  of  the  literature  on  hunger 
and  appetite  in  chap,  ii  that  most  of  the  authors  assume  a  chemical 
control  of  the  hunger  mechanism  in  the  sense  that  starvation 
changes  of  the  blood  stimulate  the  conscious  hunger  center  in  the 
brain,  the  specific  sensory  nerves  in  the  stomach,  or  sensory  nerves 
in  all  the  tissues.  We  know  now  that  the  hunger  sensation  is  caused 
by  strong  contractions  of  the  empty  or  nearly  empty  stomach. 
This  fact  modifies  but  does  not  eliminate  the  question  of  chemical 
control  of  the  hunger  mechanism.  We  must  now  determine  whether 
starvation  changes  in  the  blood  influence  the  motor  side  of  the 
mechanism,  while  the  earlier  authors  considered  the  influence  of 
the  blood  only  on  the  sensory  side  of  the  hunger  apparatus. 

Chemical  changes  in  the  blood  may  act  in  a  positive  way  either 
on  the  vagi  tonus  centers  in  the  brain  or  directly  on  the  stomach 
motor  tissues.  The  problem  of  chemical  control  of  hunger  is  thus 
resolved  into  three  main  queries,  namely:  (i)  Do  chemical  stimuli 
in  the  blood  cause  the  increased  gastric  tonus  of  hunger  ?  (2)  Do 
chemical  stimuli  in  the  blood  initiate  the  individual  gastric  hunger 
contractions  ?  (3)  Do  chemical  stimuli  control  the  grouping  of  the 
hunger  contractions  into  hunger  periods,  separated  by  periods  of 
relative  gastric  quiescence,  in  species  showing  this  grouping? 

We  must  also  consider  the  possibility  of  chemical  blood  changes 
that  may  depress  or  inhibit  the  hunger  contractions. 

The  gastric  hunger  contractions  are  inhibited  by  mechanical  and 
chemical  stimulation  of  the  nerve-endings  in  the  mucous  membrane 
of  the  mouth,  the  esophagus,  and  the  stomach.  This  insures  inhi- 
bition of  the  hunger  contractions  during  mastication  and  gastric 
digestion.  The  gastric  hunger  mechanism  receives  motor  or  tonic 
innervation  via  the  vagi,  and  the  central  connections  of  this  tonus 

217 


2i8        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

innervation  appear  to  be  practically  isolated  from  all  normal 
reflexes,  while  the  inhibitory  mechanism  via  the  splanchnic  nerves 
is  very  readily  called  into  activity  reflexly.  The  foregoing  facts 
appear  to  have  only  two  alternative  explanations,  viz:  (i)  The 
gastric  hunger  contractions  are  due  to  a  specific  automatism  (vagi 
centers  and  stomach)  primarily  independent  of  afferent  impulses 
as  well  as  the  conditions  of  the  blood.  Such  an  automatism  would, 
of  course,  vary  with  the  physiological  condition  of  the  automatic 
tissues;  but  if  this  is  the  mechanism  we  cannot  speak  of  any  physio- 
logical nervous  control  of  the  hunger  apparatus,  except  in  the  way 
of  inhibition.  (2)  The  vagi  and  the  gastric  mechanism  concerned 
in  the  genesis  of  the  hunger  contractions  may  be  influenced  in  a 
positive  way  by  physiological  changes  in  the  blood.  If  this  is  the 
case,  we  might  expect  such  changes  in  the  blood  to  be  specially 
evident  in  the  normal  animal  when  starving. 

Some  of  the  facts  already  discussed  seem  to  show  that  both  of 
the  factors  named  above  are  to  be  reckoned  with.  In  man  and  dog 
the  gastric  hunger  contractions  usually  appear  as  soon  as  the 
stomach  is  empty  of  food,  that  is,  before  intestinal  digestion  and 
absorption  of  the  meal  are  completed.  Under  these  conditions  the 
initiation  of  the  hunger  contractions  must  be  due  to  a  primary 
automatism  not  opposed  by  inhibitory  reflexes  rather  than  to  any 
changes  in  the  blood  such  as  are  presumably  involved  in  starvation, 
for  there  is  surely  no  auto-digestion  of  the  body  tissues  or  lack  of 
pabulum  in  the  body  fluids  while  normal  intestinal  digestion  and 
absorption  are  still  in  progress.  In  dogs  with  Pavlov  stomach 
pouches  we  may  also  have  hunger  contractions  in  the  main  stom- 
ach while  the  Pavlov  stomach  is  quiescent,  or  vice  versa.  On  the 
other  hand,  excessive  hemorrhage,  prolonged  starvation,  and  pan- 
creatic diabetes,  which  is  a  type  of  starvation,  lead  to  increased 
activity  of  the  hunger  mechanism,  at  least  up  to  the  point 
where  the  stomach  becomes  directly  involved  in  the  general 
debihty  and  cachexia.  The  increased  vigor  of  the  hunger  apparatus 
in  normal  individuals  as  an  after-effect  of  the  greatly  accelerated 
metabolism  caused  by  physical  exertion  and  cold,  is  a  bit  of 
evidence  pointing  in  the  same  direction. 


CHEMICAL  CONTROL  OF  THE  HUNGER  MECHANISM     219 

This  augmentation  of  the  hunger  contractions  in  starvation 
may  be  due  to  (i)  the  appearance  of  substances  in  the  blood  stimu- 
lating the  central  tonus  mechanism  or  the  peripheral  hunger 
apparatus;  (2)  the  absence  or  diminution  of  inhibitory  substances 
in  the  blood;  (3)  the  absence  or  depression  of  inhibitory  reflexes; 
(4)  starvation  changes  in  the  tissues  directly  concerned  in  the 
hunger  contraction. 

If  it  is  due  to  the  presence  of  stimulating  substances  in  the 
blood,  it  would  seem  that  transfusion  of  the  blood  of  starving 
animals  into  normal  animals  ought  to  augment  the  activity  of  the 
hunger  mechanism,  at  least  temporarily.    This  is  actually  the  case. 

II.      ACTION   OF   BLOOD   OF   STARVING  ANIMALS   ON  THE   GASTRIC 
HUNGER  MECHANISM  OF  NORMAL  ANIMALS 

Direct  transfusion  from  the  starved  donor  to  the  normal  recip- 
ient by  direct  union  of  blood  vessels  is  not  feasible,  because  if 
this  is  done  under  general  anesthesia,  the  anesthetic  itself  depresses 
the  stomach,  and  if  it  is  done  with  aid  of  local  anesthesia  only  the 
recipient  is  so  disturbed  that  the  stomach  is  inhibited  reflexly. 
But  we  found  that  good-natured  and  gentle  dogs  used  to  our 
routine  of  recording  the  gastric  hunger  contractions  were  practically 
not  disturbed  at  all  by  the  puncture  of  the  saphenous  vein  with  a 
sharp  needle  and  the  injection  of  20  to  50  c.c.  fresh-drawn  and 
defibrinated  blood.  This  technique  was  therefore  adhered  to.  In 
the  preliminary  training  of  these  dogs  the  animal's  legs  were  han- 
dled in  various  ways  (shaved,  injection  of  salt  solution,  etc.),  so 
that  the  animal  finally  paid  little  or  no  attention  to  the  handling 
of  the  leg  or  the  insertion  of  the  needle  into  the  vein.  In  some 
cases  we  decreased  the  sensitivity  of  the  skin  over  the  saphenous 
vein  by  the  application  of  carbolated  vaseline. 

The  intravenous  injection  of  20  to  50  c.c.  of  fresh  defibrinated 
blood  from  starving  dogs  into  normal  dogs  increases  the  gastric 
tonus  and  hunger  contractions  of  the  latter,  if  their  stomachs  are 
empty  and  if  moderate  tonus  and  hunger  contractions  are  in  evi- 
dence in  the  recipient  at  the  time  of  the  injection  of  the  blood.  If 
the  stomach  of  the  recipient,  although  empty  of  food,  is  atonic  and 


220        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

hunger  contractions  are  completely  absent  at  the  time  of  the 
injections,  the  blood  from  starving  animals  has  practically  no 
action  on  the  stomach.  The  stimulating  action  of  this  blood  on 
the  stomach  already  in  moderate  tonus  and  hunger  contractions 
lasts  from  lo  to  30  minutes,  depending  on  the  quantity  of  starved 
blood  injected. 

The  foregoing  conclusion  is  based  on  25  experiments  on  4 
gastric-fistula  dogs.  The  blood  for  the  transfusion  was  drawn  from 
animals  after  5  to  12  days  of  starvation. 


Fig.  27. — Tracings  from  the  empty  stomach  of  dogs.  ^,  at  an  intravenous 
injection  of  35  c.c.  blood  drawn  from  a  dog  on  the  eighth  day  of  starvation;  showing 
stimulation  of  the  gastric  hunger  apparatus,  in  the  change  from  type  I  to  type  III 
hunger  contractions  (hunger  tetanus).  B,  at  an  intravenous  injection  of  20  c.c.  of 
blood  from  a  dog  in  pancreatic  diabetes;  showing  stimulation  of  the  gastric  hunger 
mechanism  (Luckhardt  and  Carlson). 

The  failure  of  starved  blood  to  induce  tonus  and  hunger  con- 
tractions in  atonic  and  quiescent  stomachs  is  probably  due  to  the 
fact  that  by  the  present  method  of  transfusion  it  is  not  possible 
to  introduce  enough  starved  blood  to  overcome  the  inhibitory 
factors  responsible  for  the  atonic  and  quiescent  condition. 


III.      EFFECTS   OF   BLOOD   FROM  DIABETIC   ANIMALS 

Under  the  technique  described  above,  20  to  50  c.c.  of  blood 
from  animals  in  pancreatic  diabetes  and  showing  the  typical  dia- 
betic polyphagia  were  transfused  into  normal  animals.    The  results 


CHEMICAL  CONTROL  OF  THE  HUNGER  MECHANISM     221 

were  practically  identical  with  those  from  the  blood  of  starving 
animals,  that  is,  a  temporary  stimulation  of  the  gastric  hunger 
mechanism. 

From  20  to  50  c.c.  of  blood  from  normal  dogs  or  from  dogs 
whose  digestion  was  at  its  height  were  transfused  into  dogs  while 
their  gastric  tonus  and  hunger  contractions  were  being  registered. 
In  the  majority  of  these  experiments  the  transfusion  had  no  effect 
at  all  on  the  motor  condition  of  the  empty  stomach.  In  a  few 
cases  it  acted  as  a  very  slight  and  transient  stimulus,  but  in  no 
instance  did  the  blood  from  normal  animals  produce  the  marked 
effects  obtained  from  the  blood  of  starving  and  of  diabetic  animals. 
Hence  we  conclude  that  the  latter  results  are  due  to  something 
in  the  blood  of  starving  and  of  diabetic  animals  not  present,  or 
present  in  less  concentration,  in  the  blood  of  normal  animals.  It 
is  evidently  not  due  to  the  transfusion  of  the  above-named  quanti- 
ties of  defibrinated  blood  as  such,  although  defibrinated  blood 
contains  a  substance  which  induces  contraction  in  vascular  and 
intestinal  muscle.  The  intravenous  injections  of  20  to  50  c.c.  of 
0.9  per  cent  NaCl  is  also  without  effect  on  the  hunger  mechanism. 

It  is  well  known  that  intravenous  injections  of  considerable 
quantities  of  fresh  defibrinated  blood  may  cause  temporary  vaso- 
motor and  cardiac  disturbances.  Lowering  of  the  arterial  blood 
pressure  is  usually  a  feature  of  these  disturbances.  Is  vasodila- 
tion a  factor  in  the  marked  results  produced  by  blood  from  starving 
and  diabetic  animals  ?  The  following  control  tests  were  made:  A 
mixture  of  i  per  cent  peptone  in  0.9  per  cent  NaCl  was  injected 
intravenously,  and  amyl  nitrite  was  administered  by  inhalation. 
If  sufficient  peptone  or  amyl  nitrite  is  given  to  affect  the  gastric 
tonus  and  hunger  contractions,  this  effect  is  always  in  the  direction 
of  inhibition  and  paralysis.  It  is  not  clear,  however,  that  this 
inhibition  is  due  solely  to  the  vasodilation,  but  the  experiments 
show  that  a  moderate  general  vasodilation  does  not  necessarily 
lead  to  stimulation  of  the  gastric  hunger  apparatus. 

As  a  preliminary  step  in  the  analysis  of  the  stimulation  of  the 
gastric  hunger  mechanism  by  starved  and  diabetic  blood,  we  have 
tested  the  action  of  acetone  and  oxybutyric  acid  on  the  gastric 


222        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

hunger  contractions.  It  is  well  known  that  prolonged  starvation 
as  well  as  diabetes  leads  to  acidosis,  although  there  is  practically 
no  acidosis  in  pancreatic  diabetes  in  dogs  (Mario tt).  It  seemed 
possible  that  the  acetone  bodies  might  be  the  stimula^ting  factors 
in  the  starvation  and  the  diabetic  blood.  The  action  of  the  acetone 
bodies  dissolved  in  Ringer's  solution  was  tested  on  a  number  of 
animals  with  uniformly  negative  results.  That  is  to  say,  the  ace- 
tone bodies  in  concentrations  that  affect  the  gastric  hunger  appa- 
ratus at  all  cause  inhibition  and  depression.  No  indication  of  any 
primary  or  secondary  stimulation  by  the  acetone  bodies  could  be 
secured.  It  is  therefore  clear  that  the  stimulating  action  of  starva- 
tion and  diabetic  blood  on  the  hunger  mechanism  is  not  due,  at 
least  not  directly,  to  the  acetone  bodies. 

IV.      EFFECT  OF  HEMORRHAGE  ON  THE  GASTRIC  HUNGER  MECHANISM 

Some  of  the  blood  conditions  of  starvation  may  be  produced 
temporarily  by  excessive  hemorrhage.  It  is  recognized,  of  course, 
that  hemorrhage  also  introduces  factors  not  present,  at  least  in 
moderate  starvation,  such  as  the  temporary  diminution  of  hemo- 
globin. Nevertheless,  the  results  of  two  series  of  experiments  with 
the  effects  of  excessive  hemorrhage  are  so  striking  and  conclusive 
that  they  are  reported,  even  though  we  have  not  worked  out  their 
interpretation.  The  results  are  most  conveniently  stated  by  the 
following  brief  protocols: 

Dog  I.    Weight  6.0  kg. 

Oct.  20.  Types  II  and  III  gastric  hunger  contractions. 

"   21.  Type  I  contractions.     Gastric  tonus  =  3  cm.  chloroform. 

"   22.  "     I            "                     "          "     =3  cm. 

«   23.  "     I            "                     «     .     "     =3  cm. 

"   24.         "     I  "  "  "     =2icm. 

"  27.  9:12  A.M.,  light  ether  anesthesia;  146  c.c.  blood  drawn  from  carotid 
artery  at  9:30  a.m.  Recording  of  the  gastric  hunger  contractions 
began  10 :  08  a.m.  At  this  time  the  stomach  was  atonic  and  quiescent. 
A  gradual  return  of  gastric  tonus  appeared  at  10:30  a.m.  At  11  :oo 
A.M.  the  gastric  tonus  was  5  cm.  chloroform  with  vigorous  type  III 
hunger  contractions,  and  this  condition  persisted  till  the  end  of  the 
experiment  at  1 2 :  30  p.m. 


CHEMICAL  CONTROL  OF  THE  HUNGER  MECHANISM 

Oct.  28.  Type  I  contractions.  Gastric  tonus  =2|  cm.  chloroform. 

"    29.  «     I            "                    "           "     =3  cm. 

«  30.  "     I           "                    "           "     =3  cm. 

"  31.  "     I           "                    "           "     =2icm.           " 


223 


Control  Experiment  on  Dog  I 

November  18,  Ether  Anesthesia  for  20  Minutes 

Nov.  18.  Type  I  contractions  (very  feeble).    Gastric  tonus  2  cm.  chloroform. 

"     19.  "     I  contractions  (feeble) .   Gastric  tonus  2  cm.  chloroform. 

"     21.  .  "     I           "                               "          "3  cm. 

«     25.  "     I           "                               "          "     2  cm. 


26. 


II 


3t  cm. 


Dog  II.    Weight  6.7  kg. 
Oct.   30.    Type  I  hunger  contractions.     Gastric  tonus  2  cm.  chloroform. 


"    31 
Nov.    3 

"       4 

"       5 


Nov.  7. 
"  II. 
"     12. 


I 


2  cm. 


"     I  and  II  hunger  contractions.    Gastric  tonus  3  cm.  chloroform. 

"     I  hunger  contractions.  *'  ''2  cm.  " 

"I        "  "  "  "     2  cm.  " 

9: 10  A.M.,  169  c.c.  blood  withdrawn  from  carotid  artery  under  light 
ether  anesthesia.  Record  of  gastric  contractions  began  at  9:45  a.m. 
At  this  time  the  stomach  was  quiescent  with  feeble  tonus.  At 
10:00  A.M.  the  gastric  tonus  began  to  increase.  At  10:30  a.m.  the 
gastric  tonus  was  9  cm.  chloroform  with  type  III  vigorous  hunger 
contractions.  This  condition  persisted  till  the  end  of  the  experiment 
at  11:30  A.M. 
Types  II  and  III  contractions.    Gastric  tonus  2^  to  3  cm.  chloroform. 

"      II  and  III  "  "  "    3    to  7  cm. 

Type   I  «  «  u    ^Icm. 


Control  Experiment  on  Dog  II 

November  18,  Ether  Anesthesia  for  20  Minutes 

Nov.  18.  Types  I  and  III  contractions.  Gastric  tonus  i  to  4  cm.  chloroform. 

"     20.  "      I  and  III             "                  "         "      2  cm. 

"     21.  Type  I                         "                 "        "      2  cm. 

"     24.  "      I 


2  cm. 


"25.         "      III  "  "         "      3  to  4  cm. 


26.     Types  I  and  III 


3  to  6  cm. 


The  reader  will  note  that  in  both  dogs  the  hemorrhage  induced 
temporarily  a  greater  gastric  tonus  and  intensity  of  hunger  contractions 


224        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

than  those  typical  for  these  dogs  before  the  hemorrhage.  This  effect 
of  the  hemorrhage  disappears  in  less  than  24  hours.  The  controls 
show  that  the  stimulation  of  the  gastric  tonus  mechanism  is  due  to 
the  hemorrhage,  and  is  not  an  after-effect  of  the  ether  anesthesia. 
That  they  were  felt  as  hunger  contractions  by  the  dogs  was  evi- 
denced by  the  amount  of  food  consumed  on  the  hemorrhage  days. 
The  following  considerations  might  be  offered,  not  only  as  a 
possible,  but  also  as  a  probable  explanation.  The  blood  is,  of 
course,  the  purveyor  of  nutritive  substances  to  all  the  tissues  of  the 
body.    Its  chemical  composition  is  kept  remarkably  constant.    If 


Fig.  28. — A,  tracing  showing  gastric  tonus  and  type  I  hunger  contractions 
characteristic  of  dog  before  hemorrhage.  B,  record  of  gastric  tonus  contractions  of 
dog  60  minutes  after  drawing  169  c.c.  blood  from  the  carotid  artery;  showing  the 
temporary  stimulation  of  the  gastric  hunger  mechanism  as  an  after-effect  of  excessive 
hemorrhage  (bottom  of  tracing  =  0  mm.  pressure)  (Luckhardt). 

now  an  animal  is  bled  extensively  (2  to  3  per  cent  of  body  weight), 
there  is  removed  suddenly  an  enormous  amount  of  pabulum,  that 
is,  of  those  various  substances  which  are  taken  up  by  the  different 
tissues  during  circulation.  The  organs  and  tissues  deprived  of 
these  respective  nutritive  substances  become  hungry  (call  for  food) 
by  giving  up  a  something  (a  hormone)  which  acts  on  the  neuromus- 
cular apparatus  of  the  stomach  to  produce  the  hunger  contractions. 
We  recognize,  of  course,  that  acute  hemorrhage  introduces 
other  factors.  Some  of  them  have  been  mentioned.  The  explana- 
tion offered  gives  a  simple,  reasonable  picture  of  the  mechanism 
involved.  By  acute  hemorrhage  we  induce  sudden  acute  starvation. 
Probably  all  the  tissues  of  the  body  give  up  this  ''hunger  hormone." 
By  withholding  food  from  the  animal  the  blood  changes  appear 


CHEMICAL  CONTROL  OF  THE  HUNGER  MECHANISM     225 

more  slowly,  depending  for  one  thing  on  the  state  of  nutrition  and 
reserve  food  supply  of  the  animal  before  the  period  of  starvation 
is  started. 

V.      HUNGER  CONTRACTIONS   OF   THE   STOMACH  POUCH  ISOLATED 
ACCORDING   TO   THE  METHOD   OF  PAVLOV 

It  was  hoped  that  simultaneous  record  of  the  contractions  of 
the  stomach  pouch  and  of  the  main  stomach  would  throw  some 
light  on  the  relative  importance  of  the  tonus  of  the  vagi,  the  con- 
dition of  the  blood,  and  the  physiological  state  of  the  gastric  motor 
mechanisms  in  the  genesis  of  the  hunger  contractions.  The  Pavlov 
operation  leaves  the  vagi  connections  with  the  stomach  pouch  at 
least  partially  intact,  so  that  if  the  hunger  contractions  are  nor- 
mally initiated  by  efferent  vagi  impulses  we  might  expect  a  close 
parallel  between  the  rate  and  intensity  of  the  contractions  in  the 
two  stomachs.  The  character  of  the  blood  flowing  to  the  two 
stomachs  is  necessarily  the  same.  The  amount  of  local  nervous 
co-ordination  between  the  two  stomachs  depends  on  the  extent  of 
the  intact  myenteric  plexus  and  muscularis.  The  operation  severs 
by  far  the  greater  amount  of  these  neuromuscular  connections. 
This  may  diminish  the  local  nervous  co-ordination  and  thus  per- 
mit the  development  of  different  physiological  states  of  the  motor 
mechanisms  in  the  two  stomachs.  The  work  was  done  on  two  young 
and  vigorous  dogs.  Relatively  large  stomach  pouches  were  made 
according  to  the  method  of  Pavlov.  In  Dog  I  the  muscularis  join- 
ing the  two  stomachs  was  left  intact  for  a  distance  of  6  cm.  These 
figures  were  verified  by  post-mortem  examination  at  the  end  of  the 
experiment. 

Simultaneous  records  of  the  hunger  contractions  in  the  two 
stomachs  were  taken  while  the  dogs  were  lying  quietly  and  com- 
fortably in  the  lap  of  an  attendant.  The  balloon  was  passed  into 
the  main  stomach  via  the  esophagus.  The  balloon  used  for  the 
stomach  pouch  was  much  smaller  than  that  used  for  the  main 
stomach. 

Results. — Dog  I,  having  the  6  cm.  of  intact  muscularis  and 
myenteric  nerve  plexus  uniting  the  two  stomachs,  showed  a  fairly 


2  26        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

close  parallel  of  the  tonus  and  the  hunger  contractions  of  the  main 
stomach  and  the  stomach  pouch.  When  the  tonus  of  the  stomach 
was  so  great  that  the  type  III  contractions  (or  incomplete  tetanus) 
were  present,  the  synchrony  appeared  complete.  The  two  stomaclis 
gave  contractions  of  the  same  strength  and  rapidity.  The  con- 
traction and  relaxation  phases  of  the  individual  contractions  show 
also  a  fair  degree  of  correspondence. 

When  the  gastric  tonus  is  weaker,  so  that  the  stomach  exhibits 
the  slower  and  stronger  contractions  of  type  II,  the  parallel  between 
the  stomachs  is  still  in  evidence,  but  it  is  less  complete.  That  is  to 
say,  the  contractions  may  appear  simultaneously  and  be  of  corre- 
sponding strength,  they  may  appear  simultaneously  and  be  very 
unequal  in  strength,  or  there  may  be  considerable  lack  of  synchrony 
both  in  the  beginning  and  in  the  duration  of  the  contractions  of  the 
two  stomachs.  At  times  the  pouch  would  give  two  separate  and 
strong  contractions  during  a  single  but  more  protracted  contraction 
of  the  main  stomach.  When  the  contractions  are  still  slower,  or  of 
type  I,  the  co-ordination  between  the  two  stomachs  is  more  nearly 
perfect. 

Dog  II,  with  only  3  cm.  of  intact  muscularis  and  myenteric 
plexus  uniting  the  two  stomachs,  exhibited  no  synchrony  between 
the  two  stomachs  at  any  time.  The  main  stomach  would  be  quies- 
cent, while  the  pouch  showed  vigorous  hunger  contractions,  or 
vice  versa.  But  more  frequently  both  stomachs  exhibited  hunger 
rhythm  at  the  same  time,  but  without  any  synchrony  in  the  rate 
and  the  strength  of  the  contractions. 

The  Pavlov  operation  necessarily  severs  a  considerable  portion 
of  the  vagi  connection  with  the  pouch.  But  it  is  well  known  that 
at  least  half  of  the  vagus  influence  can  be  eliminated  by  section  of 
one  vagus  without  any  appreciable  disturbance  of  the  gastric  tonus. 
In  general  the  hunger  rhythm  of  the  pouch  in  Dog  II  resembled 
that  of  the  stomach  of  dogs  with  section  of  both  vagi.  In  this 
animal  (Dog  II)  the  amount  of  vagi  connections  with  the  motor 
mechanism  of  the  pouch  was  not  sufficient  to  maintain  the  normal 
tonus.  It  is  also  evident  that  the  3  cm.  bridge  of  myenteric  plexus 
was  also  insufficient  for  local  co-ordination*  of  the  two  stomachs. 


CHEMICAL  CONTROL  OF  THE  HUNGER  MECHANISM     227 

In  Dog  II,  therefore,  the  two  stomachs  dififered  in  the  quantity  of 
innervation.  The  other  obvious  differences  between  the  main 
stomach  and  the  pouch,  such  as  the  presence  of  saliva,  the  occa- 
sional presence  of  intestinal  juice  and  bile,  gases  and  food  debris, 
hair,  etc.,  were  common  for  Dogs  I  and  II.  These  conditions  were 
not  sufficient  to  create  inco-ordination  through  differences  in  the 
physiological  state  of  the  motor  mechanisms  when  the  connecting 
bridge  of  myenteric  plexus  was  6  cm.  in  length.  The  fact  that  in 
Dog  II  the  pouch  would  show  the  hunger  contractions  during 
complete  quiescence  of  the  main  stomach  and  vice  versa  seems 
to  show  that  the  physiological  state  of  the  gastric  motor  mechanism 
and  not  the  character  of  the  blood  is  the  primary  factor  in  the 
genesis  of  these  contractions.  The  main  stomach  and  the  pouch 
were  supplied  with  the  same  blood.  The  character  of  the  co- 
ordination of  the  two  stomachs  in  Dog  I  indicates  that  the  hunger 
contractions  are  not  normally  caused  by  periodic  impulses  from  the 
brain  via  the  vagi.  If  such  were  the  case  there  should  have  been  a 
closer  synchrony  of  the  contraction  and  relaxation  phases  in  the  main 
stomach  and  the  pouch.  A  primary  vagi  innervation  of  the  con- 
tractions would  not  permit  a  contraction  in  the  pouch  with  no 
contraction  in  the  main  stomach,  the  beginning  of  the  pouch  con- 
traction during  the  relaxation  phase  of  the  main  stomach,  or 
two  distinct  and  strong  contractions  of  the  pouch  during  a  single 
contraction  of  the  main  stomach.  These  results  are  readily  explain- 
able pn  the  basis  of  local  genesis  of  the  contractions  and  some 
impairment  of  the  myenteric  connections  between  the  two  parts. 
Under  these  conditions  the  physiological  state  of  the  motor  mech- 
anism of  the  two  stomachs  would  not  be  exactly  alike,  and  in  con- 
sequence there  will  be  some  interference  with,  or  inhibition  of,  the 
excitation  wave  at  the  isthmus  joining  the  two  parts,  as  well  as  in 
the  two  stomachs  themselves.  Thus  the  excitation  wave  from  the 
main  stomach  may  pass  the  myenteric  bridge  unimpeded,  but  may 
reach  the  pouch  during  the  refractory  phase  of  the  latter,  and  thus 
produce  little  or  no  effect.  And  a  similar  interference  may  obtain 
in  the  case  of  the  excitation  waves  from  the  stomach  pouch.  Since 
most  of  the  myenteric  plexus  joining  the  two  parts  of  the  stomach 


2  28        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

is  severed  in  the  Pavlov  operation,  the  local  co-ordinating  mechan- 
ism is  obviously  imparled,  although  not  completely  destroyed. 
And  if  we  assume  a  peripheral  origin  of  the  hunger  contractions, 
this  must  lead  to  a  certain  degree  of  independent  activity  of 
stomach  and  pouch.  The  results  demanded  by  this  assumption 
of  a  peripheral  stimulus  or  local  automatism  initiating  the  hunger 
contractions  are  those  actually  found  in  Dog  I,  that  is,  impaired 
synchrony  of  the  two  parts.  As  we  have  seen,  the  synchrony  of 
the  two  stomachs  is  more  nearly  perfect  the  slower  the  contractions. 
When  the  contractions  come  at  longer  intervals  there  is  less  chance 
for  interference  with  the  excitation  wave  in  the  region  of  the 
myenteric  isthmus  and  of  collision,  so  to  speak,  with  the  refractory 
state.  The  parallel  in  the  activity  of  the  two  stomachs  during 
type  III  contractions  may  be  only  apparent  or  a  parallel  of  the 
tonus  only,  for  when  the  tonus  reaches  a  certain  degree  the  con- 
tractions appear  at  their  maximum  rapidity.  Hence  if  the  main 
stomach  and  the  pouch  have  equally  strong  tonus  they  will  exhibit 
an  equal  number  of  contractions  per  unit  of  time,  even  without 
any  physiological  co-ordination  of  the  excitation  waves  between 
the  two  stomachs. 

SUMMARY 

Blood  from  starving  animals  and  animals  in  pancreatic  diabetes 
transfused  into  normal  animals  acts  as  a  temporary  stimulus  to  the 
gastric  hunger  mechanism. 

Excessive  hemorrhage  is  followed  by  a  temporary  augmentation 
of  the  gastric  hunger  contractions. 

Prolonged  starvation,  pancreatic  diabetes,  and  possibly  exces- 
sive hemorrhage  result  in  some  change  in  the  blood  that  acts  as  a 
stimulus  to  the  gastric  hunger  mechanism. 

The  character  of  the  parallel  between  the  hunger  contractions 
of  the  main  stomach  and  of  the  stomach  pouch  supports  the 
view  that  these  contractions  are  caused  primarily  by  a  gastric 
automatism  and  not  by  motor  impulses  via  vagi  nerves. 

When  the  muscularis  and  myenteric  isthmus  joining  the  main 
and  the  accessory  stomachs  is  relatively  narrow,  the  two  stomachs 


CHEMICAL  CONTROL  OF  THE  HUNGER  MECHANISM     229 

exhibit  complete  independence  of  the  hunger  contractions,  even  to 
the  point  of  vigorous  activity  of  the  one  during  quiescence  of  the 
other.  This  fact  points  to  a  local  automatism  as  a  primary  factor 
rather  than  the  condition  of  the  blood,  as  the  character  of  the 
blood  flowing  to  the  main  stomach  and  the  stomach  pouch  is 
necessarily  the  same. 

VI.      ACTION  OF  EPINEPHRIN,   PITUITRIN,    ORGAN  EXTRACTS, 
AND  DRUGS 

The  fact  that  the  gastric  hunger  contractions  involve  essentially 
the  same  motor  mechanisms  as  the  gastric  digestion  contractions 
suggests  that  the  chemical  control  exerted  by  the  blood  is  probably 
the  same  on  both.  Esserine  and  pilocarpin  augment  the  hunger 
contractions,  while  morphine  produces  profound  inhibition  (Luck- 
hard  t).  Pituitrin  produces  an  initial  augmentation;  epinephrin, 
amyl  nitrite,  calcium  chloride,  etc.,  a  temporary  depression. 

Substances  that  cause  temporary  augmentation  of  the  gastero- 
intestinal  movements  can  apparently  be  prepared  from  all  the 
tissues  of  the  body.  Attempts  have  been  made  to  show  that  there 
is  a  specific  "motor  hormone"  for  gastero-intestinal  peristalsis  in 
the  wall  of  the  digestive  tract  itself.  With  the  exception  of  epine- 
phrin it  is  probable  that  all  the  substances  so  far  studied  in  the 
various  tissue  extracts  are  abnormal  split  products  or  artifacts 
not  present  in  normal  blood,  and  hence  playing  no  r6le  either  in 
the  normal  hunger  contractions  or  in  the  digestion  peristalsis. 
Biedl  was  not  able  to  demonstrate  any  favorable  action  of  spermin 
or  testicle  extracts  on  metabolism,  appetite,  or  hunger.  The  fact 
that  a  drug  or  a  tissue  extract  when  introduced  hypodermically 
or  intravenously  initiates  or  augments  the  gastric  hunger  contrac- 
tions does  not  imply  that  these  drugs  or  extracts  have  the  same 
effect  on  the  sensation  of  hunger.  The  latter  effect  may  be  modified 
or  abolished  by  other  actions,  peripheral  and  central,  of  these 
substances. 

The  work  of  Bayliss  and  Starling,  Magnus,  Cannon,  and  others 
seemed  to  show  that  the  gastero-intestinal  contractions  are  pri- 
marily local  reflexes  through  the  Auerbach's  plexus  or  initiated  by 


230        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

''automatic"  nervous  discharges  from  the  ganglionic  plexus. 
Kieth  reports  the  presence  in  the  Auerbach's  plexus  of  ''nodal" 
tissue  similar  to  that  in  the  heart,  and  he  ascribes  the  main  role  in 
the  genesis  of  the  gastero-intestinal  movements  to  this  nodal  tissue. 
The  presence  of  nodal  tissue  in  the  Auerbach's  plexus  does  not 
materially  alter  the  problem  of  the  causation  of  the  gastero- 
intestinal  movements. 

The  special  difficulties  in  relating  the  hunger  contractions  of 
the  stomach  to  chemical  changes  in  the  blood  are  the  periodicity 
of  the  rhythm  and  the  abrupt  cessation  of  the  contraction  periods. 
So  far  as  we  know  today  chemical  changes  or  starvation  changes 
in  the  blood  are  more  continuous.  Of  course,  we  do  not  deny  the 
possibility  of  a  periodic  secretion  into  the  blood  of  some  specific 
substance  or  hormone  having  this  effect  on  the  stomach,  but  all 
the  evidence  so  far  at  hand  is  against  this  possibiHty.  The  fact 
that  after  extirpation  of  the  parathyroid  gland  there  is  a  tendency 
to  atonicity  and  motor  paralysis  of  the  gastero-intestinal  tract, 
especially  when  the  symptoms  of  tetany  are  severe,  is  no  evidence 
that  the  parathyroid  secretion  is  a  motor  stimulus  to  the  stomach 
and  intestines.  The  motor  paralysis  is  probably  due  to  secondary 
causes.  The  only  conclusion  that  seems  warranted  by  the  facts 
at  hand  is  that  the  gastric  hunger  mechanism  is  primarily  automatic 
or  independent  of  blood  changes  as  well  as  of  central  nervous 
influences;  but  in  the  normal  individual  chemical  changes  of  the 
blood  as  well  as  nervous  impulses  from  the  brain  and  spinal  cord 
augment  or  decrease  this  primary  automatism  in  a  way  to  correlate 
it  with  the  needs  of  the  organism. 

This  conclusion  should  not  be  regarded  as  a  bar  to  further 
investigation  of  the  chemical  control  of  the  hunger  mechanism  in 
health,  and  especially  in  disease.  Such  work  is  not  only  urgent,  but 
is  certain  to  yield  important  results.  Recent  experiments  by 
Dr.  Luckhardt  seem  to  show  that  the  gastric  hunger  contractions 
in  dogs  are  augmented  by  inducing  the  condition  of  phlorhizin 
glycosuria.  It  is  significant  that  all  the  conditions  which  have  so 
far  proved  to  increase  the  hunger  contractions  (diabetes  tnelHtus, 


CHEMICAL  CONTROL  OF  THE  HUNGER  MECHANISM     231 

pancreatic  diabetes,  prolonged  starvation,  great  physical  exertion, 
extreme  cold,  phlorhizin  glycosuria)  have  these  two  things  in 
common:  (i)  acidosis  of  varying  degrees,  and  (2)  either  inabihty  to 
use  sugar  by  the  tissues  or  else  a  lessened  amount  of  sugar  available 
for  the  use  of  the  tissues  because  of  the  sugar  having  been  oxidized 
or  eliminated. 


CHAPTER  XIV 

SECRETION  OF  APPETITE  GASTRIC  JUICE  IN  MAN 

I.   THE  FLUID  CONTENTS  OF  THE  STOMACH  FREE  FROM  FOOD 

The  normal  stomach,  empty  of  food,  always  contains  some  fluid 
and  mucus.  The  stomach  is  therefore,  strictly  speaking,  never 
empty.  This  fluid  in  the  empty  stomach  is  made  up  of  (i)  gastric 
juice  and  mucus,  (2)  saliva,  (3)  duodenal  contents  (pancreatic 
juice  and  bile).  Pancreatic  juice  and  bile  are  frequently  absent, 
however.  The  total  fluid  content  of  the  empty  stomach  as  well  as 
the  chemistry  of  this  fluid  depend  on  several  factors,  such  as  the 
relative  rate  of  gastric  and  salivary  secretion,  the  tonus  and  con- 
tractions of  the  stomach,  the  rate  of  absorption  in  the  stomach, 
and  the  rate  of  emptying  of  the  stomach  contents  into  the 
duodenum. 

According  to  the  more  recent  literature  the  fluid  content  of 
the  empty  stomach  of  normal  persons  varies  within  wide  limits. 
Verhagen  found  the  average  to  be  10  to  25  c.c,  but  occasionally 
as  much  as  50  c.c.  were  obtained.  Moritz  gives  higher  figures,  or 
24  to  64  c.c.  Working  on  himself,  Moritz  obtained  an  average  of 
43  c.c.  of  fluid  in  the  stomach  in  the  niorning,  with  an  acidity  of 
0.1 1  per  cent.  Rehfus,  Bergheim,  and  Hawk  state  that  in  normal 
persons  the  fluid  in  the  empty  stomach  in  the  morning  varies  from 
30  c.c.  to  180  c.c.  The  average  of  more  than  two  hundred  obser- 
vations on  our  gastric-fistula  case,  Mr.  V.,  is  20  to  25  c.c.  In  Mr.  V. 
the  salivary  factor  is  excluded  as  the  esophagus  is  completely 
closed.  The  fluid  content  in  the  stomach  in  the  morning  before 
breakfast  is  greater  than  at  noon  before  lunch.  This  is  probably 
due  to  a  lower  tonus  of  the  stomach  in  the  morning.  Sixty  tests 
on  eight  normal  medical  students  in  the  author's  laboratory  showed 
a  variation  from  10  to  120  c.c,  with  an  average  of  40  c.c.  Some 
individuals  tend  to  run  high;    others  are  consistently  low. 

232 


SECRETION  OF  APPETITE  GASTRIC  JUICE  IN  MAN       233 

II.      CONTINUOUS   SECRETION   OF   GASTRIC  JUICE  IN   THE  EMPTY 
STOMACH   OF   NORMAL*  PERSONS 

Continued  secretion  of  gastric  juice  in  the  absence  of  food  in 
the  alimentary  tract,  and  in  the  absence  of  cerebral  processes 
relating  to  appetite  (''psychic"  stimulation),  is  a  well-known 
phenomenon  in  certain  types  of  gastric  disorders,  but  it  is  generally 
assumed  by  physiologists  that,  in  the  absence  of  psychic  stimulation, 
the  gastric  glands  cease  to  secrete  almost  as  soon  as  the  stomach  is 
emptied  of  chyme,  And  that  the  glands  remain  quiescent  up  to  the 
next  feeding.  The  quiescence  is  supposed  to  be  sufficiently  com- 
plete to  render  the  surface  of  the  stomach  alkaline,  due  to  the 
continued  secretion  of  alkaline  mucus.  To  the  extent  that  this 
view  is  anything  more  than  an  assumption,  it  is  based  essentially 
on  the  studies  by  Pavlov  and  his  pupils  on  dogs.  Pavlov  frequently 
emphasizes  the  fact  that  not  a  drop  of  gastric  juice  flows  from  the 
stomach  unless  there  is  food  or  other  stimuli  in  the  stomach  or 
unless  the  appetite  is  called  into  play.  Later  Boldyreff  reported 
that  on  continued  starvation  the  gastric  glands  exhibit  periodic 
activity,  and  if  the  starvation  is  maintained  for  more  than  three 
or  four  days  the  secretion  of  the  gastric  gland  becomes  continuous. 
In  gastric-fistula  cases  of  normal  persons  no  specific  study  has 
been  made  of  the  continuous  secretory  activity  of  the  empty 
stomach,  but  in  some  instances  (Kaznelson,  Hornborg)  there  are 
indications  of  a  slow,  continued  secretion  even  when  the  stomach 
had  been  free  from  food  for  hours. 

Most  of  our  observations  on  Mr.  V.  were  made  between  10:00 
A.M.  and  4:00  P.M.,  the  usual  breakfast  of  coffee,  milk,  and  biscuits 
being  taken  at  7 :  00  a.m.  A  few  tests  were  made  between  9 :  00  a.m. 
and  12:00  M.,  and  on  such  occasions  Mr.  V.  did  not  take  any 
breakfast.  The  rate  of  the  continuous  secretion  of  gastric  juice 
in  the  empty  stomach  of  Mr.  V.  varies  from  a  few  cubic  centimeters 
up  to  60  c.c.  per  hour. 

In  general  more  gastric  juice  is  obtained  from  the  empty  stom- 
ach if  the  stomach  is  emptied  (through  the  fistula)  every  5  or  10 
minutes  than  if  it  is  emptied  every  30  or  60  minutes.  It  is  therefore 
likely  that  some  of  this  secretion  passes  into  the  intestines  or  is 


234        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

actually  reabsorbed  in  the  stomach  itself.  It  does  not  seem  prob- 
able that  the  presence  of  a  certain  amount  of  this  juice  in  the 
stomach  would  tend  to  inhibit  further  secretion. 

If  the  secretion  rate  is  low  the  acidity  is  usually  not  over  0.20 
to  0.25  per  cent,  but  the  pepsin  concentration  is  nearly  as  great  as 
that  of  the  appetite  gastric  juice.  If  the  secretion  rate  is  moderate 
the  acidity  is  greater  and  the  pepsin  concentration  may  even  exceed 
that  of  the  appetite  secretion.  When  the  secretion  rate  is  low  the 
juice  is  very  thick  and  opalescent,  owing  to  the  great  amount  of 
ropy  mucin. 

What  constitutes  the  stimulus  to  the  continuous  gastric  secre- 
tion ?  We  think  it  can  be  shown  that  it  is  not  an  appetite  secretion. 
To  be  sure,  in  the  case  of  normal  and  vigorous  persons,  periods  of 
hunger  and  appetite  are  present  almost  as  soon  as  the  stomach  is 
emptied  of  food.  And  it  is  obviously  difficult  so  to  control  the 
cerebral  processes  of  a  person  that  the  thoughts  are  not  diverted 
to  food  and  eating,  especially  if  the  usual  meal  time  has  passed  and 
one's  attention  is  at  the  time  on  the  stomach.  This  is  especially 
true  if  the  gastric  juice  is  collected  every  10  minutes.  If  the  stom- 
ach is  emptied  every  30  or  60  minutes  and  the  person  is  kept  very 
busy  with  matters  not  pertaining  to  food  and  eating,  we  think  this 
factor  is  entirely  eliminated.  This  was  done  every  day  for  two 
weeks  at  a  stretch,  so  as  to  make  it  a  mere  incident  or  routine  in 
the  day's  work.  Nevertheless,  the  continued  secretion  persisted 
with  the  usual  fluctuations  in  character  and  quantity. 

Is  the  secretion  due  to  a  subconscious  secretory  vagus  tonus  ? 
The  vagi  carry  secretory  fibers  to  the  gastric  glands.  But  we  know 
next  to  nothing  about  the  reflex  or  tonus  control  of  this  neuro- 
secretory mechanism.  We  know  that  the  vagi  send  tonus  impulses 
to  the  gastric  motor  mechanism.  But  it  does  not  follow  that  this 
is  also  the  situation  in  regard  to  the  gastric  gland. 

The  presence  of  food  in  the  intestine  may  be  partly  responsible 
for  this  continued  secretion,  by  reflex  action  from  the  intestinal 
mucosa  (Pavlov),  or  by  absorptions  of  gastric  secretins  into  the 
blood.  In  a  thirty-nine-year-old  man  with  gastric  fistula  Umber 
obtained  some  secretion  of  gastric  juice  on  rectal  feeding  with  milk, 


SECRETION  OF  APPETITE  GASTRIC  JUICE  IN  MAN       235 

sugar,  and  eggs.  Umber  explains  the  secretion  as  a  reflex  effect 
from  the  mucosa  of  the  large  intestine.  We  are  not  convinced  that 
purely  psychic  factors  are  excluded  in  his  experiments.  If  a  person 
is  hungry  it  is  likely  he  will  be  led  to  think  of  food  and  eating  by 
the  mere  act  of  rectal  feeding.  Moreover,  Umber's  experiments 
were  not  numerous  enough  really  to  establish  the  point. 

Gastric  juice  itself  contains  mucins  and  proteins  that  are 
digested  by  the  pepsin-hydrochloric  of  the  gastric  juice.  It  is 
highly  probable  that  the  products  of  this  digestion  yield  gastric 
secretagogues,  just  as  in  the  case  of  some  of  the  digestion  products 
of  the  food  proteins.  According  to  Bickel  amino-acids  given  by 
mouth  cause  secretion  of  gastric  juice.  Absorbed  slowly  in  the 
stomach  or  passed  into  the  intestines  to  be  absorbed  there,  the 
products  of  the  auto-digestion  of  the  gastric  juice  probably  furnish 
chemical  stimuli  for  a  slow  but  continuous  gastric  secretion. 
Which  one  of  these  factors  is  of  prime  importance  in  the  continuous 
secretion  of  gastric  juice  by  the  empty  stomach  must  be  determined 
by  other  lines  of  work,  especially  in  disease  conditions  where  the 
continuous  secretion  is  greatly  increased. 

III.   APPETITE  SECRETION  OF  GASTRIC  JUICE 

I .  The  mere  act  of  chewing  indifferent  substances  and  the  stimu- 
lation of  nerve-endings  in  the  mouth  by  substances  other  than  those 
directly  related  to  food  cause  no  secretion  of  gastric  juice.  On  this 
point  our  results  on  Mr.  V.  are  in  complete  accord  with  those 
obtained  from  dogs  by  Pavlov  and  his  school,  and  contrary  to  those 
of  a  number  of  observers  on  man. 

In  a  woman  with  gastric  fistula  and  esophageal  stenosis  Richet 
reports  secretion  of  gastric  juice  from  acid  stimulation  in  the  mouth. 
He  also  states  that  the  introduction  of  food  or  sapid  substances 
into  the  stomach  via  the  fistula  caused  salivation.  This  must  have 
been  a  purely  psychic  effect,  unless  the  porocedure  caused  nausea. 
The  subject  was  evidently  a  hypersensitive  woman.  We  have 
never  observed  any  of  these  effects  in  Mr.  V. 

In  1896  Schiile  introduced  the  method  of  obtaining  pure  appetite 
gastric  juice  in  man  by  emptying  the  stomach  by  means  of  a  stomach 


236 


CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 


tube,  then  chewing  food  for  15  minutes,  and  again  emptying  the 
stomach  with  the  tube.  He  claims  that  the  mere  act  of  chewing 
and  the  tasting  of  such  sapid  substances  as  oil  of  peppermint,  slices 
of  lemon,  and  mustard  cause  secretion  of  gastric  juice  even  in  the 
absence  of  appetite.  Troller,  using  Schlile's  method,  also  reports 
that  slices  of  lemon,  mustard,  etc.,  in  the  mouth,  as  well  as  the 
mere  act  of  chewing,  cause  secretion  of  gastric  juice.  In  the  majority 
of  his  experiments  the  secretion  thus  obtained  was  very  slight  (only 
about  one-fourth  that  obtained  on  chewing  bread),  and  in  some  of 


TABLE  I 
Gastric  Juice  in  c.c.  (Mr.  V.) 


Time  in  Min. 

Exp.  19 

Exp.  7 

Exp.  II 

10 

5 

I.O 

0.4 

10 

7 

0.8 

0.4 

10 

6 

05 

0.5 

10 

5 

0.4 

0.2 

10 

4 

0.4 

0-3 

10 

6 

0.4 

0.  2 

10 

5 

0.5 

03 

10 

6 

0.5 

0.4 

10 

4 

0.4 

0.  2 

10 

3 

03 

0.5 

10 

5 

0.3 

03 

10 

SO 

24.0 

17.0 

Exp.  27 


Nothing  in  mouth . 


Chewing  paraffin .  , 
Nothing  in  mouth . 
Vinegar  in  mouth . 
Nothing  in  mouth . 
Mustard  in  mouth . 
Nothing  in  mouth . 
Quinine  in  mouth . 
Nothing  in  mouth . 
Chewing  food .... 


I 

o, 
I . 
o, 
I . 
I . 
I . 
o, 
o, 
o. 
I . 
44 


the  experiments  recorded  in  detail  the  acidity  of  the  juice  is  so  low 
that  it  must  have  been  mixed  with  swallowed  saliva.  It  is  probably 
very  difficult  for  the  average  person  to  avoid  swallowing  some 
saliva  with  mustard  or  citric  acid  in  the  mouth  for  10  to  15  minutes. 
Troller  did  not  adequately  control  the  rate  of  the  continuous 
secretion  in  the  empty  stomach  when  the  persons  had  nothing  in 
particular  in  the  mouth.  Riegel  cites  the  case  of  a  professional  cook, 
in  whom  chewing  of  food  (beefsteak)  or  slices  of  lemon  caused  no 
secretion  of  gastric  juice..  This  man  showed  chronic  digestive  dis- 
orders, however.  But  Riegel  suggests  that  the  absence  of  appetite 
secretion  was  due  to  a  kind  of  permanent  fatigue  of  the  taste- 
secretory  mechanism  in  consequence  of  his  duties  as  cook.  Horn- 
borg,  working  on  a  five-year-old  boy  with  gastric  fistula  and  nearly 


SECRETION  OF  APPETITE  GASTRIC  JUICE  IN  MAN       237 

complete  cicatricial  stenosis  of  the  esophagus,  concluded  that 
chewing  indifferent,  badly  tasting,  or  strongly  tasting  (lemon) 
substances  did  not  induce  secretion  of  gastric  juice.  Umber  ob- 
tained no  gastric  secretion  by  chewing  indifferent  substances  (pieces 
of  rubber),  but  in  one  experiment  alcohol  in  the  mouth  gave  a 
slight  secretion.  It  must  be  noted  that  Umber's  subject  was  a 
man  fifty-nine  years  old,  who  might  have  been  in  the  habit  of 
taking  alcoholic  beverages  with  his  meals. 

Kaznelson  and  Bickel,  working  on  a  twenty-three-year-old  girl 
with  gastric  fistula  and  complete  cicatricial  esophageal  stenosis, 
report  that  all  sapid  substances  (quinine,  asafoetida,  etc.)  in  the 
mouth,  even  those  that  give  rise  to  disgust,  initiate  or  augment 
the  gastric  secretion.  Kaznelson  cites  one  experiment  with  quinine 
(control  experiment  with  water),  from  which  she  concludes  that 
bitter  substances  in  the  mouth  augment  the  secretion  of  gastric 
juice,  but  her  actual  figures  show,  if  anything,  the  reverse.  The 
total  secretion  of  gastric  juice  for  80  minutes  with  the  water  control 
(sham  drinking)  was  43.7  c.c,  while  the  quinine  experiment  yielded 
only  37.6  c.c.  for  the  corresponding  time. 

How  are  these  contradictory  findings  to  be  accounted  for  ?  In 
view  of  the  consistently  negative  results  of  Pavlov  and  his  students 
on  dogs,  and  of  Homborg,  and  the  writer  on  man,  it  is  our  belief 
that  the  investigators  who  report  that  mechanical  chewing  and 
general  stimulation  of  the  nerve-endings  in  the  mouth  cause  secre- 
tion of  gastric  juice  have  not  eliminated  the  factors  of  appetite, 
swallowed  saliva,  and  variations  in  the  rate  of  the  continuous 
secretion  of  the  empty  stomach.  In  man  the  appetite  factor  is  not 
easily  controlled,  except  by  a  long  series  of  tests  in  which  the  experi- 
mental procedure  becomes  a  mere  routine  to  the  subject.  There 
appears  to  be  no  direct  or  unconditional  reflex  pathway  from  the 
mouth  to  the  gastric  gland.  Unless  the  stimuli  in  the  mouth  initiate 
or  augment  the  central  processes  that  constitute  the  sensation  of 
appetite,  there  is  no  innervation  of  the  secretory  nerve-fibers  to  the 
gastric  gland. 

2.  The  relatively  slight  and  inconstant  secretion  of  gastric  juice 
produced  by  seeing,  smelling,  or  thinking  of  food. — Bringing  a  tray 


238        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

of  palatable  food  into  the  room  in  sight  of  Mr.  V.  has  never  yet 
caused  secretion  of  gastric  juice,  no  matter  what  the  degree  of 
hunger  and  appetite.  It  is  probable  that  under  these  conditions 
the  primary  and  normal  effects  of  seeing  and  smelling  the  food  are 
inhibited  by  the  consciousness  of  the  experiment,  or  possibly  his 
main  interest  was  not  the  food,  but  the  expiration  of  the  experiment 
so  that  he  might  partake  of  the  food.  In  order  more  closely  to 
approximate  normal  conditions,  Mr.  V.  was  sent  out  to  the  near-by 
cafeteria  to  select  the  lunch  that  he  knew  he  would  eat  shortly 
after  returning  with  it  to  the  laboratory.  The  rate  of  his  gastric 
secretion  was  measured  for  lo-minute  periods  before  going  for 
the  food,  during  the  selection  of,  and  after  returning  to  the  labora- 
tory with  it.  In  the  majority  of  these  tests  the  act  of  selecting  the 
ingredients  for  the  noonday  meal  caused  a  slight  and  temporary 
augmentation  of  the  secretion  rate  of  the  empty  stomach.  On 
the  whole  this  augmentation  was  greater  the  greater  the  rate  of 
the  continuous  secretion.  But  on  some  days  the  augmentation 
was  absent,  although  Mr.  V.  was  in  good  health,  felt  hunger,  and 
the  cafeteria  displayed  the  usual  variety  of  food. 

Pavlov  reports  that  there  are  great  individual  variations  in  dogs 
in  the  amount  of  gastric  secretion  induced  by  seeing  and  smelling 
food.  This,  in  all  likelihood,  is  true  of  man,  and  we  suspect  that 
Mr.  V.  belongs  to  the  group  of  individuals  in  whom  the  taste  of 
the  food  is  the  all-important  factor  in  the  psychic  secretion  of 
gastric  juice.  We  have  not  been  able  appreciably  to  augment  the 
continuous  secretion  in  Mr.  V.  by  inducing  the  thought  of  food, 
for  example,  during  a  test  while  he  is  busy  with  other  work,  by 
arresting  his  attention  casually,  and  by  discussing  with  him  the 
taste  and  ingredients  of  his  favorite  dishes. 

Schiile  states  that  seeing  or  smelling  food  causes  no  secretion  of 
gastric  juice  in  normal  persons.  This  is  directly  contradicted  by 
Bulawinzew.  This  investigator  emptied  the  stomach  by  means  of 
the  stomach  tube,  then  let  the  subject  see  or  smell  food,  and  again 
emptied  the  stomach.  The  gastric  juice  thus  obtained  had  such 
low  acidity  (0.2  per  cent  HCl)  that  it  must  either  have  been  in  the 


SECRETION  OF  APPETITE  GASTRIC  JUICE  IN  MAN       239 

continuous  gastric  secretion  or  the  appetite  gastric  juice  mixed 
with  saHva.  There  is  nothing  in  the  review  to  indicate  that  he 
controlled  the  continuous  gastric  secretion.  Homborg  obtained 
no  secretion  of  gastric  juice  from  a  five-year-old  boy  on  his  seeing 
or  smelling  food,  probably  because  the  child  always  became  angry 
when  not  permitted  to  eat  the  food  shown  him.  Cade  and  Latarjet 
report  secretion  of  gastric  juice  was  induced  by  talking  to  the 
subject  about  her  favorite  food.  This  subject  (a  young  woman)  is 
exceptional  in  that  she  virtually  had  an  accessory  stomach,  but 


TABLE  II 

Secretion  of  Gastric  Juice  (Mr.  V.)  on  Seeing,  Smelling,  and 
Thinking  of  Food  when  Hungry 


Time 

IN 

Gastric  Juice  in  c.c. 

Mm. 

Exp.  3 

Exp.  8 

Exp.  1 2 

Exp.  IS 

Exp.  30 

Exp.  45 

10 

5 

o.S 

0.3 

0.4 

0.6 

0.4 

10 

7 

0.3 

0.4 

0.5 

o.S 

0.3 

10 

6 

05 

0-3 

0.4 

0.4 

0.4 

Selecting  the  lunch  at  the  cafe-l 
teria | 

10 

14 

I.O 

I.O 

3-5 

o.S 

I.O 

10 

10 

I.O 

0.6 

2.0 

0.4 

I.O 

10 

5 

O.S 

o-S 

0.3 

I.O 

10 

6 

03 

0.4 

0.4 

0.7 

the  mucosa  of  the  isolated  stomach  portion  was  directly  exposed 
so  that  the  collection  of  the  secretions  was  rather  difficult.  Kaz- 
nelson  and  Bickel,  working  with  a  twenty-three-year-old  girl  with 
gastric  fistula  and  stenosis  of  the  esophagus,  reached  the  remarkable 
conclusion  that  anything  which  stimulated  the  olfactory  sense 
induced  secretion  of  gastric  juice  in  the  resting  stomach.  Thus 
they  claim  that  smelling  ammonia,  acidic  acid,  and  aromatic  oils 
causes  secretion  of  gastric  juice.  This  we  are  absolutely  unable 
to  confirm  on  Mr.  V.  It  is  possible  that  in  this  young  woman 
every  gustatory  and  olfactory  stimulus  when  manipulated  by  the 
investigators  led  to  thoughts  of  food  through  idea  associations. 


240        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

IV.      GASTRIC   SECRETION   INDUCED   BY   TASTING   AND   CHEWING 
PALATABLE   FOOD 

I.  The  secretion  rate. — We  have  records  of  156  tests  of  the 
appetite  secretion  of  Mr.  V.  during  the  20  minutes'  mastication 
of  the  noonday  meaL  The  particular  ingredients  of  this  meal  were 
of  his  own  selection,  and  varied  from  day  to  day.  The  meal  usually 
included  soup  and  some  kind  of  meat  and  gravy,  and  always  milk 
and  a  dessert.  Secretion  of  gastric  juice  during  20  minutes'  masti- 
cation of  palatable  food  was:  lowest,  30  c.c;  highest,  156  c.c; 
average,  70  c.c;  number  of  experiments,  156. 


/ 

^ 

\ 

IS 

iO 

/ 

\ 

\ 

s 

/ 

' 

\ 

\, 

0 

/ 

\ 

Chewing  food 

Fig.  29. — Typical  curve  of  secretion  of  gastric  juice  of  Mr,  V.  on  mastication  of 
palatable  food  for  20  minutes.  The  gastric  juice  was  collected  at  5 -minute  intervals. 
The  rise  in  the  secretion  rate  during  the  last  5  minutes  of  mastication  is  due  to  chewing 
the  dessert  (fruit). 

This  gives  an  average  rate  of  secretion  of  3.5  c.c.  of  gastric 
juice  per  minute.  The  maximum  rate  of  secretion  determined  at 
any  time  was  54  c.c.  in  5  minutes,  or  10.8  c.c.  per  minute;  the 
lowest  was  7  c.c.  in  5  minutes,  or  1.4  c.c.  per  minute.  The  secre- 
tion rate  is  proportional  to  the  palatability  of  the  food.  Thus  the 
secretion  rate  is  nearly  always  highest  in  the  last  5 -minute  period, 
when  Mr.  V.  masticates  the  dessert,  and  on  the  day  when  the 
highest  rate  of  secretion  was  noted  (156  c.c.  in  20  minutes)  Mr.  V. 
stated  that  the  lunch  was  ''unusually  fine." 

Is  this  rate,  and  quantity  of  appetite  secretion  of  gastric  juice 
typical  for  normal  adults  ?    Mr.  V.  is  in  normal  health,  except  for 


SECRETION  OF  APPETITE  GASTRIC  JUICE  IN  MAN       241 

infrequent  periods  of  headache  and  nervousness,  the  etiology  of 
which  is  obscure.  Troller  reports  5  experiments  on  a  person  with 
nervous  dyspepsia.  Chewing  beefsteak  for  15  minutes  yielded  55 
c.c.  of  gastric  juice,  while  3  experiments  on  a  person  with  hyper- 
acidity gave  50  c.c.  gastric  juice  in  15  minutes.  This  is  a  secretion  of 
a  rate  of  about  3.5  c.c.  per  minute.  Chewing  bread  for  15  minutes 
yielded  much  less  gastric  juice.  In  the  case  of  persons  with  hypo- 
chlorhydria  the  average  secretion  for  15  minutes  (chewing  beef- 
steak) was  only  28  c.c.  In  Umber's  fistula  case  (a  man  fifty-nine 
years  old)  two  tests  with  chewing  beefsteak  for  15  minutes  yielded 


TABLE   III  , 

Rate  of  Appetite  Secretion  of  Gastric  Juice  of  Mr.  V. 
Detail  of  Typical  Experiments 


Rate  of  Secretion  of  Gastric  Juice  in  Consecutive  s-Min.  Periods,  c.c. 

Experiment 
No. 

Before  Starting 
Chewing 

During  Chewing 

On  Cessation  of 
Chewing 

20 

31 

35 

55 

86 

94 

120 

150 

I 

0.5 
0.3 
0.  2 
0.  2 
0.2 
0.2 

05 

o"6 
2.0 
0.  2 

03 
0.2 

0.3 

0.8 

30 

03 
0.2 
0. 1 

0.  2 

10 
II 

15 
20 

5 

6 

6 

22 

15 
18 
16 
22 
20 
II 
28 
54 

:^ 

15 
21 
18 

15 
20 

35 

20 

23 
18 

30 
20 
12 
29 
45 

5 

10 
8 
15 
9 
3 
8 
20 

3 
6 

4 
6 

3 

2 

6 

15 

I.O 

2.0 

1-5 
6.0 
1.0 

05 
2.0 
8.0 

73  c.c.  and  48.5  c.c.  gastric  juice  in  60  minutes.  This  low  rate  of 
secretion  (about  i  c.c.  per  minute)  must  be  due  to  the  advanced 
age  and  to  a  malignant  tumor  of  the  esophagus.  The  ten-year-old 
girl  studied  by  Sommerfeld  secreted  no  to  150  c.c.  gastric  juice 
in  90  minutes  on  chewing  meat  or  mixed  food  for  30  to  40  minutes, 
a  secretion  rate  of  2  to  2.5  c.c.  per  minute.  The  maximum  secre- 
tion rate  in  the  twenty-three-year-old  girl  studied  by  Kaznelson 
and  Bickel  was  5  c.c.  per  minute,  the  average  secretion  rate,  being 
much  lower.  Hornborg's  five-year-old  boy  secreted  15  to  25  c.c. 
in  30  minutes  on  chewing  meat  or  apple  pie.  Chewing  bread  or 
milk  yielded  less  than  half  this  amount.  The  three-year-old  child 
observed  by  Bogen,  on  chewing  meat  for  15  minutes,  yielded  6  to 


242        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

22.5  c.c.  gastric  juice,  or  an  average  rate  of  less  than  i  c.c.  per 
minute. 

These  data  reported  by  previous  investigators  cannot  be  directly 
compared  with  our  results  on  Mr.  V.  for  the  reason  that  the  col- 
lection of  the  gastric  juice  was  not  always  confined  to  the  actual 
period  of  mastication  of  the  food.  The  rate  of  the  appetite  secretion 
starts  to  fall  almost  as  soon  as  Mr.  V.  ceases  to  masticate  the  food, 
and  in  15  minutes  the  activity  of  the  gastric  glands  is  in  most  cases 
down  to  the  level  of  the  continuous  secretion.  The  secretion  rate 
is  highest  during  the  actual  tasting  of  the  food. 

In  this  respect  there  is  a  marked  difference  between  man  and 
dog.  In  the  dog,  after  12  to  24  hours  of  starvation,  sham  feeding 
with  meat  for  5  minutes  may  initiate  and  keep  up  secretion  of  gastric 
juice  for  3  to  6  hours  (Pavlov,  Rosemann).  It  is  obvious  that  in 
these  tests  on  dogs  the  starvation  period  was  much  longer  and  the 
hunger  and  appetite  more  intense  than  in  our  experiments  on  Mr.  V. 
Another  factor  is  probably  the  greater  voluntary  control  over 
attention  and  other  cerebral  processes  in  man. 

It  may  be  of  interest  in  this  connection  to  note  the  rates  of 
gastric  secretion  that  have  been  obtained  by  sham  feeding  in  dogs. 
Konowaloff  reports  4  c.c.  per  minute;  Schoumow-Simanowsky 
found  a  maximum  of  5  c.c.  per  minute;  and  Rosemann  (in  a  dog 
weighing  24  kg.)  gives  as  the  average  3.4  c.c.  per  minute.  Since 
the  quantity  of  gastric  glands  even  in  very  large  dogs  is  probably 
only  a  third  of  that  in  the  adult  man,  the  foregoing  data  seem  to 
indicate  that  the  gastric  glands  in  dogs  work  with  greater  speed 
than  the  gastric  glands  of  man. 

2.  The  direct  relation  between  the  rate  of  appetite  gastric  secretion 
and  the  palatahleness  of  the  food. — The  mastication  of  bread  and 
butter  or  the  taking  of  milk  in  the  mouth  yields  much  less  gastric 
juice  than  the  chewing  of  meat.  This  is  in  line  with  results  of 
previous  observers  on  man.  The  taste  nerve-endings  are  evidently 
stimulated  more  intensely  by  the  readily  diffusible  sapid  substances 
in  the  meat.  In  general  the  desserts  (pies,  pudding,  fruits)  yielded 
even  greater  secretion  than  meat.  This  was  particularly  noticeable 
in  the  case  of  chewing  oranges.    Mr.  V.  is  especially  fond  of  oranges. 


SECRETION  OF  APPETITE  GASTRIC  JUICE  IN  MAN       243 

The  sapid  substances  in  the  orange  juice  probably  diffuse  readily 
and  thus  reach  all  the  taste  nerve-endings  in  marked  concentration. 
There  is  no  question  but  that  the  mastication  of  a  palatable  dessert 
at  the  end  of  a  meal  serves  to  augment  and  prolong  the  appetite 
secretion  of  gastric  juice. 

3.  The  latent  period  of  the  gastric  appetite  secretion. — Pavlov 
and  his  coworkers  found  that  the  appetite  gastric  secretion  in  dogs 
exhibited  uniformly  a  latent  period  of  5  to  6  minutes.  According 
to  the  literature  the  latent  period  of  the  appetite  gastric-juice 
secretion  in  man  varies  from  3  to  9  minutes.  The  latent  period 
depends  primarily  on  the  condition  of  the  gastric  glands.  Thus 
if  there  is  a  continuous  gastric  secretion  of  2  to  6  c.c.  per  10  minutes 
at  the  time  mastication  of  the  food  begins,  the  appetite  secretion 
shows  practically  no  latent  period  at  all.  The  quantity  of  gastric 
juice  secreted  during  the  first  5  minutes  of  chewing  is  just  as  great 
as  that  secreted  during  the  second  or  third  5 -minute  periods.  On 
the  other  hand,  if  the  continuous  secretion  is  very  low  (0.2  to  0.3  c.c. 
per  10  minutes)  the  appetite  secretion  shows  a  latent  period  of  2 
to  4  minutes.  It  is  therefore  evident  that  with  the  gastric  secretion 
already  in  progress  the  appetite  secretion  reflex  exhibits  no  greater 
latent  time  than  neuromuscular  reflexes  in  general. 

The  latent  period  varies  indirectly  with  the  intensity  of  the 
appetite  stimulation.  If  the  continuous  secretion  is  very  low,  the 
latent  period  of  the  secretion  does  not  exceed  2  to  3  minutes,  provided 
the  food  is  very  palatable. 

v.     TOTAL  SECRETION  OF  GASTRIC  JUICE  IN  MAN  ON  AN  AVERAGE  MEAL 

As  stated  above,  Mr.  V.  yields  appetite  gastric  juice  at :  mini- 
mum secretion  rate,  84  c.c.  per  hour;  maximum  secretion  rate, 
648  c.c.  per  hour;  average  secretion  rate,  210  c.c.  per  hour.  Does 
this  furnish  us  a  clew  to  the  total  gastric  secretion  on  an  average 
meal  in  man  ?  This  question  cannot  be  answered  by  direct  meas- 
urements," even  in  cases  of  duodenal-  fistula  and  collection  of  all  the 
chyme  issuing  through  the  pyloric  opening,  as  the  alimentary  tract 
of  such  persons  is  far  from  normal,  and  we  still  have  the  variable 
factors  of  swallowed  saliva  and  of  direct  absorption  in  the  stomach. 


244        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

In  the  case  of  dogs  sham  feeding  alone  may  yield  600  to  700  c.c. 
of  gastric  juice  in  4  to  6  hours.  But  this  situation  is  abnormal 
because  the  sham  feeding  does  not  satisfy  the  appetite,  even  though 
the  secretion  inhibits  the  hunger.  It  is  therefore  certain  that  the 
appetite  secretion  is  much  less  when  the  food  is  permitted  to  reach 
the  stomach.  But  when  the  food  is  allowed  to  reach  the  stomach, 
how  can  we  measure  the  total  gastric  secretion  ?  Using  large  dogs 
with  fistula  of  duodenum,  Moritz  reports  that  the  ingestion  of 
200  gm.  of  meat  caused  a  secretion  of  320  c.c.  gastric  juice  in  7 
hours.  Part  of  this  was  undoubtedly  swallowed  saliva,  and  possibly 
some  admixture  of  bile  and  pancreatic  juice.  With  the  same  method 
Tobler  obtained  200  to  300  c.c.  of  gastric  juice  from  feeding  100  gm. 
meat;   part  of  this  fluid  was  undoubtedly  swallowed  saliva. 

It  seems  to  us  that  we  can  arrive  at  a  very  close  estimate  of  the 
total  average  secretion  of  gastric  juice  in  a  m^n  on  the  following 
basis :  Pavlov  and  his  pupils  have  shown  on  dogs  that  the  secretion 
curves  of  the  main  and  the  accessory  stomach  pouch  run  parallel. 
They  have  also  shown  that  on  a  meal  of  meat,  or  a  mixed  meal, 
the  secretion  usually  reaches  the  maximum  toward  the  end  of  the 
first  or  during  the  second  hour.  Lonnquist  notes  particularly  that 
the  secretion  does  not  reach  its  maximum  until  toward  the  end  of 
the  second  hour  after  eating.  On  the  whole,  the  quantity  of  gastric 
juice  yielded  by  a  dog's  accessory  stomach  after  the  first  two  hours 
following  a  moderate  meal  of  meat,  bread,  or  a  mixture  of  meat 
and  bread,  is  about  half  of  that  secreted  during  the  entire  digestion 
period.  This  is  evident  from  experiments  reported  in  detail  by 
Pavlov  and  his  students,  as  well  as  from  studies  on  dogs  in  our  labo- 
ratory. But  this  is  not  true  if  a  very  large  quantity  of  food  is  given, 
or  if  the  food  contains  a  considerable  amount  of  fat,  as  in  both 
cases  the  secretion  of  fluid  is  greatly  prolonged. 

We  can  safely  assume  that  the  general  relations  and  the  relative 
importance  of  the  appetite  and  the  hormone  gastric  juice  are  the 
same  in  man  and  dog.  Pflaunder  supports  the  view  that  the  maxi- 
mum rate  of  secretion  in  man  is  reached  at  the  end  of  the  first  or 
the  beginning  of  the  second  hour  of  digestion.  Sick  finds  that 
the  maximum  acidity  of  gastric  content  is  usually  reached  at  the 


SECRETION  OF  APPETITE  GASTRIC  JUICE  IN  MAN       245 

end  of  the  first  hour  of  digestion.  The  same  is  shown  by  the  more 
recent  studies  of  Rehfus,  Bergheim,  and  Hawk,  using  the  Ewald 
rest  meal  on  normal  persons. 

The  total  secretion  of  gastric  juice  in  normal  adult  man  on  inges- 
tion of  the  average  dinner  of  meat,  bread,  vegetables,  coffee  or  milk, 
and  dessert  will,  on  the  foregoing  assumptions,  be  as  follows:  ist 
hour,  200  c.c.  gastric  juice;  2d  hour,  150  c.c;  3d  to  5th  hours, 
350  c.c;  total,  700  c.c.  gastric  juice. 

It  should  be  noted  in  this  connection  that  Mr.  V.'s  noonday 
meal  is  in  reality  the  big  meal  or  dinner.  He  secretes  less  gastric 
juice  on  his  evening  meal,  probably  not  more  than  400  to  500  c.c, 
and  from  the  fact  that  he  makes  his  breakfast  solely  on  biscuits, 
coffee,  and  milk  it  is  likely  that  his  secretion  of  gastric  juice  on  the 
morning  meal  does  not  exceed  250  to  300  c.c  This  would  make 
a  total  of  1,350  to  1,500  c.c.  of  gastric  juice  secreted  in  24  hours. 
These  figures  do  not  include  the  continuous  secretion  in  the  absence 
of  food.  It  is  of  interest  to  note  that  Pflaunder  arrived  at  practically 
the  same  figures  (1,500  c.c.  or  25  c.c.  per  kg.  of  body  weight  in 
24  hours),  basing  his  estimate  on  calculations  from  the  acidity  and 
volume  of  the  gastric  content  at  varying  periods  after  the  meal. 
'  It  need  not  be  pointed  out  that  the  foregoing  figures  are  subject 
to  great  variations,  depending  on  the  condition  of  the  stomach  and 
the  quality  and  quantity  of  the  food. 

SUMMARY 

The  fluid  contents  of  the  "empty"  stomach  vary  from  nothing 
up  to  150  c.c.  The  average  of  a  number  of  tests  varies  with  the 
individual  from  30  to  50  c.c  The  quantity  is  greater  in  the  morn- 
ing than  at  noon  or  at  6:00  p.m.  It  is  on  the  whole  greater  in  the 
summer  than  in  the  winter  months.  The  most  important  factor 
in  these  daily  and  seasonal  variations  is  probably  the  tonicity  of 
the  empty  stomach  and  the  rate  of  the  continuous  secretion. 

The  gastric  glands  in  the  normal  person  are  never  completely 
quiescent.  The  continuous  secretion  varies  from  2  to  50  c.c.  per 
hour.  The  higher  figures  are  exceptional,  but  may  obtain  for 
several  days  in  succession,  again  to  revert  to  the  lower  figures. 


246        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

The  vagus  secretory  tonus  is  a  possible  and  the  auto-digestion  of 
the  gastric  juice  itself  is  a  probable  factor  in  this  continuous  gastric 
secretion.  The  secretion  itself  is  rich  in  pepsin,  but  when  the 
secretion  rate  is  very  low  it  is  poor  in  free  hydrochloric  acid. 

Chewing  on  indifferent  substances  and  stimulation  of  the  nerve- 
endings  in  the  mouth  by  substances  not  related  to  food  do  not 
cause  secretion  of  gastric  juice,  that  is,  these  processes  do  not 
augment  the  continuous  gastric  secretion. 

Seeing,  smelling,  and  possibly  thinking  of  palatable  food  usually 
cause  a  very  slight  and  transitory  secretion  of  gastric  juice. 

The  rate  of  secretion  of  gastric  juice  on  mastication  of  palatable 
food  is  directly  proportional  to  the  palatability  of  the  food.  During 
mastication  the  average  rate  is  3.5  c.c.  per  minute  (minimum  rate: 
1.4  c.c;  maximum  rate:  10.8  c.c).  On.  cessation  of  chewing  the 
secretion  rate  diminishes  rapidly,  so  that  in  15  to  20  minutes  the 
gastric  glands  reach  the  level  of  the  continuous  gastric  secretion. 
The  chemistry  of  this  appetite  gastric  juice  is  practically  constant. 

The  latent  period  of  this  appetite  secretion  varies  indirectly 
with  the  rate  of  the  continuous  secretion,  so  that  when  the  con- 
tinuous secretion  is  abundant  the  appetite  secretion  shows  prac- 
tically no  latent  period  at  all,  while  with  the  lowest  rate  of  the 
continuous  secretion  the  latent  period  varies  from  2  to  3  minutes. 
This  latent  period  is  therefore  one  of  the  processes  in  the  gland 
cells,  and  not  in  the  nervous  mechanism. 

On  the  basis  of  these  experiments  on  Mr.  V.,  on  the  reports  of 
other  gastric  fistula  cases  in  man,  and  on  the  work  of  Pavlov  on 
dogs,  it  is  estimated  that  an  adult  normal  person  secretes  on  an 
average  meal  (dinner)  700  c.c  of  gastric  juice,  or  an  average  total 
of  1,500  c.c.  of  gastric  juice  in  24  hours. 

On  the  whole,  this  work  on  the  appetite  secretion  of  gastric 
juice  in  man  confirms  and  extends  the  work  of  Pavlov  and  his 
pupils  on  dogs.  Pavlov  overlooked  or  ignored  the  continuous 
secretion  in  the  absence  of  all  food  and  psychic  stimuli,  and  he 
put  too  great  an  emphasis  on  the  secretion  induced  in  a  hungry 
animal  by  seeing  and  smelling  food.  The  significant  appetite  secre- 
tion in  man  is  that  induced  by  tasting  and  chewing  good  food.    The 


SECRETION  OF  APPETITE  GASTRIC  JUICE  IN  MAN      247 

continuous  secretion  does  not  fit  in  with  Pavlov's  general  theory  of 
strict  adoption  of  the  digestion  juices  to  the  food,  as  it  apparently 
serves  no  useful  purpose  in  digestion. 

It  is  also  clear  that  Pavlov  overestimated  the  importance  of 
the  appetite  secretion  in  gastric  digestion.  The  continuous  secre- 
tion initiates  gastric  digestion  in  the  absence  of  appetite  juice. 
Dogs  with  both  vagi  sectioned  exhibit  practically  normal  gastric 
digestion  within  a  few  days  after  the  operation,  despite  the  fact 
that  the  appetite  gastric  juice  is  eliminated.  Cats  may  be  forcibly 
fed  with  unpalatable  food  and  the  stomach  digestion  is  practically 
as  rapid  as  when  they  eat  voluntarily.  And  we  know  that  in  man 
the  pepsin-hydrochloric  acid  of  the  gastric  juice  may  be  greatly 
reduced  if  not  entirely  absent  (achylia)  without  marked  impair- 
ment of  gastric  peristalsis  or  food  utilization.  We  have  on  numer- 
ous occasions  removed  all  the  appetite  gastric  juice  from  Mr.  V.'s 
stomach  before  the  masticated  meal  was  put  into  his  stomach 
without  producing  the  slightest  evidence  of  indigestion. 

The  significance  of  hunger  and  appetite  for  digestion  is  appar- 
ently not  so  much  in  the  actual  yield  of  appetite  gastric  juice  as 
in  the  fact  that  when  these  sensation  complexes  are  present  the 
entire  gastero-intestinal  tract,  both  on  the  motor  and  on  the 
secretory  side,  is  in  fit  condition  to  handle  the  ingested  food. 


CHAPTER  XV 
THE  CHEMISTRY  OF  HUMAN  APPETITE  GASTRIC  JUICE 
I.      THE    SOLIDS 

The  total  solids  of  the  pure  gastric  juice  of  Mr.  V.  vary  from 
0.48  gm.  to  0.58  gm.  per  100  c.c,  of  which  0.34  gm.  to  0.47  gm. 
is  organic,  and  o.ii  gm.  to  0.14  gm.  inorganic  material.  The 
hydrochloric  acid  is,  of  course,  expelled  in  the  evaporation  and 
drying  of  the  gas  trie- juice  residue. 

The  hunger  gastric  juice  (continuous  secretion)  is  distinctly 
higher  than  the  appetite  juice  both  in  total  and  in  organic  solids. 

The  gastric  juice  or  fluid  in  the  empty  stomach  is  distinctly 
more  dilute  than  the  appetite  juice,  although  it  may  approach  the 
concentration  of  the  latter  in  cases  where  the  rate  of  the  continuous 
secretion  is  considerable. 

The  foregoing  figures  on  Mr.  V.'s  appetite  gastric  juice  are 
slightly  higher  than  those  given  by  Sommerfeld  for  the  gastric  juice 
from  a  ten-year-old  girl,  namely  0.40  gm.  to  0.47  gm.  Schmidt 
found  in  a  human  gastric-fistula  case  0.58  gm.  of  total  solids  in  the 
gastric  juice,  of  which  0.32  gm.  was  organic,  and  0.26  gm.  inorganic. 
But  Schmidt  did  not  work  with  pure  gastric  juice.  This  is  evident 
from  his  method  of  obtaining  the  juice,  as  well  as  from  the  fact  that 
the  acidity  of  the  juice  was  only  0.20  gm.  or  less  than  half  that  of 
normal  human  gastric  juice.  Albu  reports  one  experiment  on  a 
patient  with  hypersecretion  finding  the  percentage  of  solids  only 
0.24  gm.,  practically  all  of  which  (0.23  gm.)  was  inorganic  salts. 
He  also  reports  one  determination  on  normal  human  gastric  juice 
(pure  appetite  juice)  in  which  the  inorganic  solids  were  0.18  gm.; 
the  organic  solids  are  not  given. 

Our  results  on  Mr.  V.  agree  closely  with  most  of  those  reported 
for  the  gastric  juice  of  dogs.  The  total  concentration  of  organic 
and  inorganic  substances  is  therefore  about  the  same  in  the  normal 
gastric  juice  (appetite  juice)  of  man  and  dog. 

248 


CHEMISTRY  OF  HUMAN  APPETITE  GASTRIC  JUICE      249 
II.      SPECIFIC   GRAVITY 

The  specific  gravity  of  Mr.  V.'s  appetite  gastric  juice  varies 
between  1,006  and  1,009  with  an  average  of  1,007.  This  is  the 
average  of  twenty  tests  on  an  equal  number  of  gastric-juice  samples. 
It  will  thus  be  seen  that  1,009  i^  ^^  exceptional  concentration. 

The  specific  gravity  of  the  continuous  secretion  is  higher  than 
that  of  the  fluid  or  juice  found  in  the  empty  stomach  and  lower 
than  that  of  the  appetite  juice. 

The  specific  gravity  of  the  appetite  gastric  juice  of  the  dog,  as 
reported  by  Schoumow-Simanowski,  Konovaloff,  Friedenthal,  and 
Rosemann  varies  from  1,002  to  1,007,  with  an  average  of  1,004. 
This  low  average  figure  is  probably  due  to  the  fact  that  in  most  of 
these  experiments  the  gastric  juice  was  collected  for  several  hours 
after  only  a  few  minutes  of  sham  feeding.  There  is  evidence  that 
the  percentage  of  solids  in  the  gastric  juice  is  greatest  during  the 
first  hours  of  appetite  or  digestion  secretion.  The  concentration 
of  the  dog's  appetite  gastric  juice  during  the  first  20  minutes  of 
secretion  will  in  all  probability  be  found  identical  with  that  of  man 
for  the  same  period. 

III.      OSMOTIC   CONCENTRATION 

The  appetite  gastric  juice  lowers  the  freezing-point  from 
—0.55°  C.  to  —0.62°  C;  the  continuous  secretion  from  —0.47°  C. 
to  —0.52°  C;  the  fluid  of  the  empty  stomach  from  —0.21°  C. 
to  —0.41°  C.  The  juice  found  in  the  empty  stomach  exhibits 
the  greatest  fluctuations  in  osmotic  pressure,  the  appetite  and  the 
hunger  juice  being  very  constant.  The  hunger  juice  has,  on  the 
whole,  a  lower  osmotic  concentration  than  the  appetite  juice. 

The  foregoing  figures  for  the  appetite  gastric  juice  of  Mr.  V. 
are  practically  identical  with  those  reported  on  the  pure  gastric 
juice  of  other  human  fistula  cases.  Sommerfeld  (in  a  ten-year-old 
girl)  found  the  freezing-point  to  vary  from  —0.47°  C.  to  — o.  65°  C; 
Kaznelson  (twenty-five-year-old  girl)  reports  a  variation  from 
—0.46°  C.  to  —0.54°  C.  Umber  reports  two  tests  on  the  gastric 
juice  (pure)  of  a  fifty-nine-year-old  man  with  cancer,  finding  a 


250        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

variation  of  —0.15°  C.  to  —0.82''  C.  Assuming  that  Umber's 
determinations  are  correct,  the  gastric  juice  of  this  cancer  patient 
was  clearly  not  normal.  We  question  whether  the  normal  stomach 
can  secrete  a  juice  with  an  osmotic  concentration  so  much  greater 
than  the  blood  as  the  figure  —0.82°  C.  demands.  The  reader  will 
note  that  the  figures  of  Sommerfeld  and  Kaznelson,  as  well  as  our 
own  for  Mr.  V.,  indicate  an  osmotic  pressure  of  the  appetite  gastric 
juice  not  far  below  or  above  that  of  the  human  blood.  According 
to  Bickel  the  gastric  juice  (ten-year-old  child)  is  always  hypotonic 
to  the  blood.  Lehman  concludes  that  the  osmotic  pressure  of 
normal  gastric  juice  (gastric  content)  is  usually  less  than  —  0.50°  C, 
and  that  a  concentration  above  this  figure  indicates  hyperacidity 
or  other  pathological  conditions.  This  view  is  obviously  unten- 
able. 

The  osmotic  concentration  of  the  dog's  appetite  gastric  juice 
is  practically  identical  with  that  of  man.  Sasaki  reports  a  variation 
from  —0.51°  C.  to  —0.60°  C;  Rosemann  gives  somewhat  higher 
figures,  or  —0.56°  C.  to  —0.64°  C.  On  the  other  hand,  Bickel 
reports  extraordinary  fluctuations  in  osmotic  concentration  of 
dogs'  gastric  juice  (Pavlov  pouch)  or  —0.52°  C.  to  —1.21°  C.  We 
question  whether  the  normal  stomach  can  secrete  a  juice  of  the 
osmotic  concentration  —1.21°  C,  that  is,  twice  that  of  the  blood. 

IV.      TOTAL  NITROGEN   OF   THE   GASTRIC  JUICE 

The  total  nitrogen  was  determined  by  the  method  of  Kjeldahl 
on  9  different  lots  of  appetite  gastric  juice  of  Mr.  V.  The  average 
of  all  our  determinations  is  0.60  gm.  nitrogen  per  100  c.c.  appetite 
juice.  The  total  nitrogen  of  the  hunger  juice  was  not  determined. 
If  all  the  nitrogen  is  in  the  form  of  proteins,  and  if  we  accept  the 
figures  of  Nencki  and  Sieber,  and  of  Pekelhaaring,  namely,  that 
nitrogen  constitutes  14.39  per  cent  of  the  proteins  of  the  gastric 
juice,  the  appetite  gastric  juice  of  man  would  contain  on  the  average 
nearly  0.42  gm.  protein  per  100  c.c,  or  practically  all  the  organic 
solids  in  the  appetite  juice. 

Rosemann  reports  nitrogen  determinations  in  2  lots  of  dog's 
appetite  gastric  juice,  finding  0.035  gm.  and  0.054  gm.  per  100  c.c, 


CHEMISTRY  OF  HUMAN  APPETITE  GASTRIC  JUICE      251 

respectively.     These  figures  are  considerably  lower  than  ours  on 
the  appetite  juice  of  Mr.  V. 

V.      AMMONIA 

The  ammonia  of  the  fresh  gastric  juice  was  determined  by  a 
combination  of  Folin's  aeration  and  the  Nessler  colorimetric  meth- 
ods, using  I  to  5  c.c.  of  the  juice.  The  ammonia  cannot  be  deter- 
mined by  the  Nessler  reagent  directly  in  pure  gastric  juice,  as 
parallel  tests  on  the  same  samples  of  gastric  juice  yield  higher 
figures  by  aeration  and  Nessler  than  by  Nessler  direct  (using  i  c.c. 
of  the  juice). 

Ammonia  in  the  amounts  of  2  to  3  gm.  per  100  c.c.  is  a  constant 
constituent  of  pure  gastric  juice  of  man  and  dog.  The  ammonia 
appears  to  be  slightly  more  concentrated  in  the  continuous  secre- 
tion or  hunger  juice  than  in  the  appetite  juice.  The  ammonia  may 
be  greatly  increased  in  gastric  ulcers,  and  in  certain  normal  persons 
the  ammonia  may  also  be  exceptionally  high  (10  to  15  mgr.). 

Rosenheim  and  Strauss  reported  small  amounts  of  ammonia  in 
the  gastric  content  of  man.  Zunz,  working  with  the  gastric  content 
(test  meals)  on  normal  persons  and  on  persons  with  various  dis- 
orders of  the  alimentary  tract,  also  reports  the  presence  of  ammonia. 
In  the  normal  individuals  the  ammonia  of  the  test-meal  contents 
varied  from  0.7  to  5.0  mgr.  per  100  c.c.  In  cancers  of  the  stomach 
the  ammonia  in  the  test-meal  content  was  increased.  The  test 
meal  introduces  factors  (bacterial  action,  saliva,  etc.)  not  present 
in  pure  gastric  juice.  Sommerfeld,  working  with  pure  gastric  juice 
of  a  ten-year-old  girl  with  complete  stricture  of  the  esophagus, 
states  that  gastric  juice  contains  no  ammonia.  Nencki,  Zaleski, 
and  Salaskin  reported  4  to  5.5  mgr.  ammonia  per  100  c.c.  pure 
gastric  juice  of  the  dog.  Rosemann  reports  the  constant  presence 
of  a  small  amount  of  ammonia  in  the  pure  gastric  juice  (appetite 
secretion)  in  the  dog.  Reisner  concludes  that  the  ammonia  in 
gastric  juice  comes  from  the  saliva. 

What  is  the  origin  and  significance  of  the  gastric-juice  ammonia  ? 
It  is  known  that  saliva  contains  traces  of  ammonia.  We  find  that 
the  mixed  saliva  of  man  contains  from  0.5  to  1.5  mgr.  ammonia 


252        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

per  loo  c.c.  Salaskin  found  2.5  gm.  NH3  per  100  c.c.  in  the  saliva 
of  the  dog.  But  in  dogs  with  Pavlov's  stomach  pouch,  and  in  our 
gastric-fistula  case,  Mr.  V.,  no  sahva  can  enter  the  stomach  or  the 
part  of  the  stomach  yielding  the  juice. 

The  ammonia  of  the  duodenal  content  may  be  a  factor,  as 
Boldyreff  and  others  have  shown  the  frequency  with  which  intes- 
tinal content  enters  the  stomach.  This  factor  is  excluded  in  dogs 
with  the  Pavlov  stomach  pouch.  In  our  human  fistula  case  this 
factor  is  readily  controlled  by  making  the  ammonia  determinations 
only  on  those  samples  of  gastric  juice  that  are  absolutely  free  from 
admixture  with  bile,  pancreatic  juice,  and  succus  entericus.  Rose- 
mann  points  out  that  the  gastric-juice  ammonia  cannot  be  a  simple 
filtrate  from  the  blood  since  normal  blood  contains  only  about  0.5 
mgr.  of  ammonia  per  100  c.c. 

Huber,  working  in  the  author's  laboratory,  found  that  intra- 
venous and  oral  administration  of  ammonia  salts  increases  the 
ammonia  concentration  in  the  gastric  juice.  It  is  decreased  on 
low,  and  increased  on  high  protein  diet.  But  when  the  urine 
ammonia  is  greatly  decreased  by  taking  alkalies,  or  greatly  in- 
creased by  taking  acids,  the  concentration  of  the  gastric- juice 
ammonia  remains  unchanged. 

The  question  of  the  origin  of  the  gastric-juice  ammonia  is 
therefore  very  complex,  (i)  It  is  in  part  an  active  excretion  from 
the  blood.  (2)  It  may  be  formed  in  part  by  deamidization  of 
amino-acids  in  the  gastric  mucosa.  (3)  It  may  be  formed  in  the 
process  of  secretion  of  gastric  juice,  or  (4)  by  the  action  of  the  HCl 
on  the  gastric-juice  protein,  or  on  the  cells  of  the  mucosa.  In. 
cases  of  gastric  ulcers  of  infectious  origin  it  may  come  in  part  from 
bacterial  activity  in  the  active  focus  of  the  ulcer. 

In  1898  Nencki,  Pavlov,  and  Zaleski  found  that,  per  unit  of 
mass,  there  is  more  ammonia  in  the  gastric  mucosa  than  in  any 
other  tissue  of  the  body.  These  findings  were  essentially  confirmed 
by  Salaskin  the  same  year.  Huber  found  a  greater  concentration 
of  ammonia  in  the  fundic  mucosa  than  in  the  mucosa  of  the  cardiac 
and  the  pyloric  ends  of  the  stomach.  These  facts  seem  to  indicate 
some  relation  of  the  ammonia  formation  to  the  secretion  process 


CHEMISTRY  OF  HUMAN  APPETITE  GASTRIC  JUICE       253 

itself  and  to  the  protein  absorption,  unless  the  higher  ammonia  con- 
tent of  the  secreting  and  absorbing  mucosa  represents  ammonium 
chloride  in  the  process  of  absorption  from  the  gastric  juice. 

VI.      THE  AMINO-ACIDS 

When  deductions  are  made  for  the  ammonia  nitrogen  of  the 
juice,  the  formol- titrable  nitrogen  of  Mr.  V.'s  appetite  gastric  juice 
varied  from  3  to  9  gm.  nitrogen  per  100  c.c.  The  gastric  juice  of  a 
second  fistula  case  (Mr.  E.)  gave  7  gm.  per  100  c.c.  Four  lots  of 
dog's  appetite  gastric  juice  (Pavlov  pouch)  gave  only  i  to  2  gm.  of 
amino-acid  nitrogen.  It  thus  appears  that  normal  human  gastric 
juice  contains  slightly  more  amino-acid  than  ammonia  nitrogen; 
but  the  greater  part  of  the  gastric-juice  nitrogen  is  associated  with 
more  complex  proteins. 

Zunz  reports  that  the  amino-acid  nitrogen  (test  meals)  usually 
exceeds  the  ammonia  nitrogen,  and  that  both  substances  are 
increased  in  cases  of  gastric  cancer.  In  three  normal  persons  the 
maximum  amino-acid  was  10  gm.  per  100  c.c.  of  gastric  content, 
while  in  several  gastric  cancer  cases  it  reached  15  to  20  gm.  per 
100  c.c.  of  content.  But  these  figures  cannot  be  directly  compared 
with  ours  on  pure  gastric  juice,  because  of  the  uncertain  factors 
associated  with  the  gastric  contents  following  a  test  meal. 

VII.      AUTO-DIGESTION   OF   THE   GASTRIC  JUICE 

When  fresh  gastric  juice  is  incubated  at  38°  C.  the  following 
changes  take  place  in  the  proteins  and  the  gastric  mucin : 

1.  Practically  all  the  ropy  mucin  and  mucin  flocculi  are  dis- 
solved. 

2.  The  pink  color  of  the  biuret  reaction  is  increased.  In  fact, 
fresh  human  gastric  juice  gives  practically  a  violet  biuret  reaction, 
and  this  color  is  intensified  and  changed  toward  pink  by  the 
auto-digestion. 

3.  The  characteristic  protein  precipitation  at  the  point  of 
neutralization  is  decreased. 

4.  The  quantity  of  proteins  precipitated  by  nitric  acid  and  by 
heat  is  reduced. 


254        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

It  is  thus  clear  that  the  protein  of  pure  gastric  juice  undergoes 
pepsin-hydrochloric  acid  digestion  in  the  stomach  itself.  But 
some  of  the  gastric  juice  proteins  are  not  hydrolyzed,  at  least  not 
down  to  the  peptone  stage.  It  is  an  interesting  fact  that  the  pro- 
tein of  the  gastric  juice  of  man  injected  into  guinea-pigs  sensitizes 
the  animals  to  subsequent  injections  of  human  serum,  but  injec- 
tions of  even  large  quantities  of  human  gastric  juice  into  pigs  thus 
sensitized  produce  no  anaphylaxis.  This  auto- digestion  of  the  gas- 
tric juice  itself  is  probably  a  factor  in  the  continuous  secretion  of 
gastric  juice  in  the  way  of  yielding  gastric  secretagogues. 

VIII.      ACIDITY   OF  NORMAL   GASTRIC  JUICE  '      ' 

The  acidity  was  determined  by  titration  with  A^/40  NaOH, 
and  using  dimethyl-amino-azo-benzene  and  phenothalein  as  indi- 
cators for  the  free  and  the  total  acidity,  respectively.  During  the 
4  years  that  Mr.  V.  has  been  under  observation  hundreds  of 
determinations  have  been  made  of  the  acidity  of  the  contents  of 
the  ''empty"  stomach,  of  the  hunger  juice,  or  continuous  secre- 
tion, and  of  pure  appetite  juice.  The  reader  will  recall  that  the 
contents  of  the  "empty"  stomach  are  taken  one  hour  after  wash- 
ing out  the  stomach  with  200  c.c.  of  water.  All  the  cases  where 
the  gastric  juice  oi*  gastric  content  was  contaminated  with  bile 
(intestinal  content)  are  excluded  from  the  summaries  given  in 
Table  IV. 

The  second  gastric-fistula  case,  Mr.  E.,  was  a  man  of  twenty-six 
years  of  age,  healthy  and  vigorous.  Nearly  a  year  prior  to  our 
work  on  him  his  esophagus  was  corroded  with  a  solution  of  lye, 
and  this  led  to  a  nearly  complete  cicatricial  stenosis,  and  hence 
the  gastrostomy.  At  the  time  of  the  observations  the  esophagus 
had  been  dilated  sufficiently  to  permit  swallowing  of  any  well- 
masticated  food,  and  the  gastrostomy  opening  was  used  only  in 
the  dilation  processes.  In  this  case,  saliva  is  therefore  not  excluded 
from  the  contents  of  the  empty  stomach,  and  possibly  not  from 
the  continuous  or  hunger  secretion,  although  Mr.  E.  was  instructed 
and  urged  not  to  swallow  any  saliva  during  these  experiments. 
The  appetite  juice  was  obtained  by  Mr.  E.'s  chewing  palatable 


CHEMISTRY  OF  HUMAN  APPETITE  GASTRIC  JUICE      255 

food,  and  spitting  out  the  chewed  food,  care  being  taken  not  to 
swallow  saliva  or  particles  of  food. 

These  results  from  my  two  gastric-fistula  cases  are  in  agreement 
with  the  work  of  Pavlov  and  his  pupils  on  dogs,  and  the  work  of 
previous  observers  on  pure  gastric  juice  of  normal  persons.  The 
latter  data  have  recently  been  brought  together  and  discussed  by 
Boldyreff. 

TABLE  IV 

Acidity  of  Normal  Human  Gastric  Juice 


Material 

No.  OF 

Obser- 
vations 

Acidity 

•  Person 

Free 

Total 

fCont.  empty  stomach. 

]  Hunger  juice 

[Appetite  juice 

f Cont.  empty  stomach . 

j  Hunger  juice 

[Appetite  juice 

235 
180 

28s 

10 

8 

IS 

Low 

High 

Aver. 

Low 

High 

Aver. 

Mr.  V... 
Mr.  E... 

0. 10 
0.15 
0-35 

0.09 
0.20 
0.30 

0.3s 
0.35 
0.44 

0.36 
0.32 
0.36 

0.18 
0.2s 
0.40 

0.20 
0.25 
0.34 

015 
0.20 
0.40 

0.18 
0.27 
0.36 

0.40 
0.4S 
0.53 

0.41 
0.38 
0.47 

0.23 

034: 
0.48 

0.2s 

0-33 
0.44 

Normal  human  gastric  juice  (appetite  secretion)  when  secreted 
above  a  certain  minimum  rate  shows  a  practically  constant  total 
acidity  of  nearly  0.5  per  cent  HCl,  or  the  same  as  the  gastric 
juice  of  normal  dogs.  Practically  the  same  figure  is  obtained  when 
the  acidity  is  determined  by  conductivity  methods  (Men ten). 
The  gastric  juice  (appetite  as  well  as  hunger  juice)  secreted  by  the 
normal  stomach  at  a  low  rate  shows  lower  than  normal  acidity 
and  total  chlorides.  The  view  of  Pavlov  based  on  experiments 
on  dogs  that  gastric  juice  is  secreted  at  uniform  and  constant  acidity 
is  true  for  man  only  in  regard  to  appetite,  digestion,  and  hunger 
juice  secreted  at  fairly  high  rate.  We  must  take  cognizance  of  the 
equally  important  fact  that  the  normal  gastric  mucosa  is  capable 
of  secreting  a  juice  of  submaximal  acidity. 

The  studies  of  Rehfus  and  Hawk  on  the  acidity  of  the  gastric 
content  at  varying  periods  after  drinking  water  and  ingesting  an 


2S6        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

Ewald  test  meal  also  support  the  view  that  the  normal  gastric 
juice  has  a  fairly  constant  acidity. 

The  reader  will  note  that  normal  human  gastric  juice  is  equal  in 
total  acidity  to  the  maximum'  acidity  reported  by  clinical  observers 
for  so-called  hyperacidity  in  man.  So  far  as  we  are  acquainted  with 
the  literature,  there  is  no  evidence  that  the  gastric  glands  under  any 
pathological  conditions  are  able  to  or  do  secrete  a  juice  of  higher  than 
normal  acidity.  Actual  hyperacidity  does  not  occur  in  cases  of 
experimental  ulcers  in  the  stomach  and  duodenum.  But  there 
may  be  hypersecretion.  Moreover,  the  presence  in  the  stomach 
of  gastric  juice  of  full  acid  strength  leads  by  itself  and  immediately 
to  no  untoward  symptoms. 

The  contents  of  the  ''empty"  stomach,  and  the  continuous  or 
hunger  secretion  (when  the  secretion  rate  is  low)  have  uniformly  a 
lower  acidity  than  the  appetite  juice.  The  total  acidity  of  contents 
of  the  ''empty"  stomach  is  0.2  or  less.  The  reader  will  note  that 
this  figure  is  frequently  given  as  the  acidity  of  pure  gastric  juice  of 
normal  persons.  The  acidity  of  the  continuous  or  hunger  secretion 
is  higher,  and  the  greater  the  secretion  rate  the  higher  the  acidity 
until  it  may  equal  that  of  the  appetite  juice.  In  no  instance  does 
the  acidity  of  the  continuous  secretion  exceed  that  of  the  appetite 
juice. 

What  is  the  cause  of  the  low  acidity  of  the  continuous  secretion 
and  contents  of  the  empty  stomach  ?  The  following  factors  must 
be  taken  into  account: 

I.  The  actual  acidity  of  the  juice  as  secreted  may  increase  with 
the  secretion  rate,  until  the  maximum  acidity  is  reached  with  the 
high  average  rate  of  secretion,  under  conditions  similar  to  those 
obtaining  in  the  case  of  the  salivary  glands  where  the  concentration 
of  the  salts  and  the  organic  materials  increases  with  the  rate  of 
saHvary  secretion.  If  this  is  a  factor  the  gastric  juice  secreted  at  a 
low  rate  should  show  a  lower  osmotic  concentration  and  a  smaller 
total  of  chlorides  than  the  juice  secreted  at  high  rate.  The  figures 
reported  by  Umber  for  man  and  by  Rosemann  for  the  dog  support 
this  view,  the  former  investigator  showing  particularly  that  the 
osmotic  concentration  of  the  gastric  juice  increases  with  the  rate 


CHEMISTRY  OF  HUMAN  APPETITE  GASTRIC  JUICE       257 

of  secretion.  The  cryoscopic  data  may,  however,  be  misleading, 
as  the  salts  produced  by  the  neutralization  of  the  HCl  may  not 
dissociate  as  freely  as  the  acid. 

2.  The  slower  rate  of  secretion  may  give  a  chance  for  the  HCl 
to  be  partly  neutralized  by  the  alkaline  mucus  secreted  by  the 
mucin  cells  of  the  gastric  mucosa.  This  is  the  factor  emphasized  by 
Pavlov.  In  fact,  Pavlov  takes  the  position  that  in  the  normal 
animal  gastric  juice  has  practically  a  constant  acidity,  irrespective 
of  the  secretion  rate,  but  the  actual  acidity  of  the  juice  in  the 
cavity  of  the  stomach  is  purely  a  matter  of  rate  of  neutralization. 
If  this  is  the  sole  factor,  the  total  chlorides  of  the  gastric  juice 
ought  to  show  a  greater  constancy  than  the  acidity.  That  the 
hydrochloric  acid  of  the  gastric  juice  is  in  part  neutralized  by  the 
gastric  mucus  is  obvious.  But  according  to  Boldyreff  the  alkalinity 
of  gastric  mucus  is  only  0.05  to  o.io  Na2C03.  That  is  to  say,  it 
would  require  100  to  200  c.c.  of  gastric  mucus  to  reduce  100  c.c.  of 
gastric  juice  from  the  normal  acidity  of  0.45  down  to  0.25  by  neutral- 
ization and  dilution.  The  importance  of  this  factor  has  therefore 
been  overestimated  by  Pavlov. 

3.  When  the  gastric  juice  is  collected  from  a  Pavlov  accessory 
stomach,  or  from  an  individual  with  complete  closure  of  the  esoph- 
agus, as  is  the  case  with  Mr.  V.,  the  saliva  cannot  be  a  factor  in 
lowering  the  gastric  juice  acidity  by  neutralization  and  dilution. 
When  all  or  most  of  the  saliva  is  swallowed  the  acidity  of  the  gastric 
juice  is  necessarily  reduced  in  proportion  to  the  relative  rate  of 
salivary  and  gastric  secretion.  This  is  effected  by  dilution  rather 
than  by  neutralization,  as  the  titration  alkalinity  of  saliva  is  low 
(0.8  Na^COj;  Neumeister,  cited  by  Boldyreff). 

According  to  Boldyreff,  Carlson,  Hicks  and  Visher,  Rehfus  and 
Hawk,  an  important  factor  in  lowering  the  acidity  of  gastric  juice 
from  that  actually  secreted  by  the  gland  (0.5)  to  that  usually 
found  in  the  cavity  of  the  stomach  (0.25),  is  the  entrance  of  the 
alkaline  intestinal  contents  (pancreatic  juice,  bile,  and  ^uccus 
entericus)  into  the  stomach.  This  usually  occurs,  probably,  when 
the  acid  in  the  stomach  mounts  much  above  0.25.  This  "mechan- 
ism for  self-regulation  of  the  acidity  of  the  stomach  content'* 


258        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

probably  breaks  down  in  cases  of  so-called  ''hyperacidity"  in  man. 
In  cases  of  "hypersecretion"  the  quantity  of  juice  secreted  is 
greater  than  normal,  and  the  secretion  may  persist  in  the  absence 
of  all  normal  stimuli,  but  the  neutraliziag  factors  suffice  to  reduce 
the  acidity  of  the  juice  approximately  to  that  found  in  the  normal 
stomach.  It  is  purely  a  balance  of  secretion  rate  and  of  neutraliza- 
tion capacity.  linpairment  of  the  neutralization  factors  or  a  very 
excessive  secretion  rate  of  gastric  juice,  or  pyloric  obstruction 
would  tend  to  render  the  acidity  of  the  gastric  content  equal  to 
that  of  pure  gastric  juice;  in  other  words,  produce  clinical  "hyper- 
acidity." 

IX.      TOTAL  CHLORIDES 

The  total  chlorides  of  the  appetite  gastric  juice  of  Mr.  V.  are 
very  constant,  the  minimum  being  0.49  per  cent  and  the  maximum 
0.56  per  cent  chlorine.  The  continuous  secretion  or  hunger  juice 
is  more  variable  in  chloride  content,  and  this  variation  appears  to 
be  directly  dependent  on  the  secretion  rate  and  on  the  acidity. 
In  general,  the  lower  the  secretion  rate  the  lower  are  the  acidity 
and  the  total  chlorides.  This  is  in  agreement  with  the  findings  of 
Foster  and  Lambert  on  dogs. 

These  facts  seem  to  point  to  the  conclusion  that  the  low  acidity 
of  the  gastric  juice  secreted  at  a  slow  rate  is  not  due  entirely  to 
neutralization.  We  have  apparently  a  secretion  of  gastric  juice 
of  an  acidity  actually  lower  than  that  of  the  rapidly  secreted 
appetite  juice.  The  dependence  of  the  actual  secreted  acidity  on 
the  secretion  rate  is  not  a  very  close  one,  however,  as  we  may  have 
very  marked  fluctuation  in  rate  without  any  change  in  chlorides. 
But  below  a  certain  secretion  rate  (25  to  30  c.c.  per  hour  from  the 
entire  stomach  of  the  adult)  an  actual  hypoacid  juice  is  secreted. 

The  foregoing  figures  for  total  chlorides  in  the  normal  gastric 
juice  of  Mr.  V.  agree  closely  with  the  findings  of  previous  observers 
on  the  gastric  juice  of  dog  and  of  man.  Rosemann  gives  0.54  to 
0.64  CI  for  the  appetite  gastric  juice  of  the  dog.  The  figures  given 
by  Sommerfeld  for  human  appetite  juice  vary  from  0.53  to  0.59  CI. 
Umber,  working  on  an  old  man  (fifty-nine  years)  with  partial  eso- 


CHEMISTRY  OF  HUMAN  APPETITE  GASTRIC  JUICE      259 

phageal  stenosis  (malignant),  reports  total  chlorides  of  the  gastric 
juice  as  varying  from  0.27  to  0.60  CI. 

X.   CONCENTRATION  OF  PEPSIN 

In  our  tests  the  digestion  mixture  was  made  up  of  i  c.c.  gastric 
juice  and  15  c.c.  N/10  HCl.  The  Qgg  albumin  in  the  Metts  tubes 
was  coagulated  ii  boiling  water  for  10  minutes.  The  digestion 
time  was  24  hours  at  37°  C.  Under  these  conditions  the  pepsin 
concentration  of  the  gastric  juice  of  Mr.  V.  showed  the  following 
figures:  appetite  juice,  6^  to  7I  mm.  digestion;  continuous  secre- 
tion, 6  to  7  mm.  digestion;  contents  of  empty  stomach,  3  to  4  mm. 
digestion.  The  results  are  stated  in  the  length  of  albumin  column 
actually  digested,  because,  according  to  Cobb,  the  law  of  Schiitz 
does  not  hold  for  pepsin  in  concentrations  that  digest  more  than 
4  to  5  mm.  in  24  hours. 

The  appetite  gastric  juice  of  Mr.  E.,  our  second  gastric-fistula 
case,  when  tested  as  above  in  14  experiments,  showed  a  pepsin 
concentration  of  5  to  7  mm.  with  an  average  of  6  mm.,  a  slightly 
lower  value  than  the  gastric  juice  of  Mr.  V.  The  pepsin  concen- 
tration of  the  gastric  juice  of  normal  dogs  runs  somewhat  lower, 
or  2  to  5  mm. 

When  the  Metts  tubes  are  placed  in  16  c.c.  of  undiluted  human 
gastric  juice  (appetite  secretion)  the  digestion  in  24  hours  at  37°  C. 
varies  from  12  to  16  mm.,  or  only  twice  the  quantity  digested  in 
the  dilution  of  i  c.c.  juice  to  15  c.c.  N/10  HCl.  This  seems  to 
indicate  that  in  normal  gastric  juice  the  pepsin  is  present  in  excess 
of  the  needs  or  at  least  far  in  excess  of  that  needed  in  economic 
digestion. 

The  U.S.  Pharmacopeia  defines  "100  per  cent  pepsin  as  a 
preparation  capable  of  digesting  three  thousand  times  its  own 
weight  of  finely  divided  tgg  white  (coagulated)  in  three  hours." 
The  Pharmacopeia  test  is  carried  out  as  follows :  10  gm.  of  boiled 
white  of  egg  is  macerated  through  a  No.  40  filter  and  placed  in 
40  c.c.  0.3  per  cent  HCL,  3J  mgr.  dried  pepsin  added,  and  the 
mixture  incubated  at  52°  C.  for  3  hours,  with  occasional  stirring. 
After  being  treated  in  this  manner,  there  is  only  a  very  small  residue 


26o        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

of  undissolved  egg  white  at  the  end  of  three.hours,  but  the  procedure 
of  measuring  the  amount  of  this  residue  does  not  yield  very  accurate 
results. 

This  test  was  applied  to  six  different  lots  of  appetite  gastric 
juice  of  Mr.  V.  Under  the  foregoing  conditions,  i  to  i|  c.c.  appetite 
gastric  juice  digested  lo  gm.  of  coagulated  and  finely  divided  egg 
white  in  3  hours  practically  as  completely  as  is  done  by  3I  mgr. 
"  100  per  cent  pepsin."  As  defined  by  the  U.S.  Pharmacopeia,  i  c.c. 
of  human  gastric  juice  must  therefore  contain  3I  mgr.  pepsin,  or 
100  c.c.  of  the  juice,  35  mgr.  pepsin.  We  have  seen  that  the  appetite 
gastric  juice  of  man  contains  about  400  mgr.  organic  material  per 
100  c.c.  That  is,  according  to  the  Pharmacopeia  definition,  only 
about  10  per  cent  of  the  organic  matter  in  the  human  gastric  juice 
is  pepsin. 

It  has  been  shown  that  an  adult  normal  person,  if  hungry, 
secretes  600  to  700  c.c.  gastric  juice  after  an  average  palatable 
dinner,  or  a  total  of  about  1,500  c.c.  gastric  juice  in  24  hours.  That 
is  to  say,  there  is  a  secretion  of  240  to  250  mgr.  pepsin  per  dinner, 
capable  under  proper  conditions  of  digesting  from  630  gm.  to  750 
gm.  of  protein  (coagulated  and  finely  divided  egg  albumin)  in  3 
hours;  and  the  total  pepsin  secretion  in  24  hours  is  525  mgr. 
capable  of  digesting  i^  kg.  proteins  (coagulated  egg  white)  in  3  hours. 

It  is  therefore  clear  that  the  normal  human  stomach  secretes 
pepsin  far  in  excess  of  the  actual  needs  of  gastric  digestion,  or,  more 
precisely,  far  in  excess  of  what  can  be  used  advantageously  under 
ordinary  conditions  of  gastric  digestion.  When  the  boiled  egg 
white  is  broken  up  in  larger  pieces,  such  as  occurs  in  ordinary  rapid 
mastication,  i  c.c.  of  gastric  juice  requires  6  to  10  hours  for  complete 
digestion. 

This  great  excess  of  pepsin  in  normal  gastric  juice  probably 
explains  the  clinical  findings  of  great  reduction  in  pepsin  content 
without  any  evidence  of  impaired  gastric  digestion.  It  probably 
also  explains,  in  part  at  least,  the  practical  uselessness  of  commercial 
pepsin  as  a  therapeutic  measure  in  gastric  disorders. 


CHAPTER  XVI 
HUNGER  AND  APPETITE  IN  DISEASE 
I.      ANALYSIS   OF   THE  PROBLEM 

We  believe  all  physicians  will  agree  that  the  control  of  hunger 
and  appetite  is  a  very  important  factor  in  the  control  of  disease, 
and  especially  of  chronic  disorders.  The  physiologist  is  therefore 
assured  of  the  co-operation  of  the  clinics  in  the  investigation  of 
the  pathology  of  hunger  and  appetite.  Such  co-operation  is  a  sine 
qua  non  for  progress  in  this  field,  as  the  final  verdict  in  the  analysis 
of  the  pathology  of  hunger  is  the  word  and  the  reactions  of  the 
patient  himself. 

Conditions  of  disease  in  man,  so  far  as  they  affect  hunger, 
usually  involve  a  decrease  or  absence  of  hunger  and  appetite 
sensations,  as  in  fevers,  anemias,  cachexias,  and  neuroses  of  various 
origin.  Certain  pathological  states  such  as  diabetes,  brain  tumors, 
neuroses,  etc.,  may  be  associated  with  abnormally  strong  hunger 
and  appetite.  In  diseases  of  the  stomach  itself  the  hunger  sensa- 
tion may  be  decreased  (atony,  gastritis,  constipation,  etc.),  increased 
(hypermotility,  pyloric  insufficiency,  vagotonia,  etc.),  or  altered  in 
the  direction  of  abnormal  painfulness,  as  in  gastric  and  duodenal 
ulcers. 

From  our  analysis  of  the  nature  of  the  hunger  mechanism,  it  is 
evident  that  depression  or  absence  of  the  hunger  sensation  may 
theoretically  be  brought  about  in  any  one  of  the  following  ways: 
(i)  direct  failure  or  absence  of  the  tonus  and  hunger  contractions 
of  the  empty  stomach;  (2)  prolonged  reflex  inhibition  of  the 
stomach;  (3)  interference  with  or  depression  of  the  central  con- 
duction paths;  (4)  direct  depression  of  the  cerebral  or  thalamic 
hunger  centers;  (5)  interference  with  the  central  conduction  of 
the  hunger  impulses  by  abnormal  or  unusually  strong  impulses 
from  other  proprioceptors.  These  various  conditions  may  be 
caused   by   pathological    changes   in    the   blood,    in    the    motor 

261 


262        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

mechanism  of  the  stomach  itself,  or  in  the  central  conduction  paths 
and  sensory  centers.  Pathological  augmentation  of  hunger  would 
result  from  the  reversal  of  these  conditions.  The  first  question 
that  must  be  settled  in  the  physiological  pathology  of  hunger  is 
whether  or  not  the  abnormalities  are  due  to  changes  in  the  gastric 
hunger  mechanism  itself.  This  can  in  every  case  be  settled  by  direct 
tests  on  the  patient,  using  our  balloon  method.  When  the  patho- 
logical changes  are  in  the  central  nervous  system  itself  their  analysis 
becomes  much  more  difficult. 

II.      THE   LITERATURE   ON  HUNGER  AND  APPETITE   IN 
DISEASE   IN  MAN 

I.  Bulimia. — Abnormally  intense  hunger  sensation  has  been 
termed  bulimia.  Some  authors  do,  others  do  not,  distinguish 
between  bulimia  and  polyphagia.  When  distinctions  are  made, 
the  term  polyphagia  is  used  to  denote  the  condition  of  excessive 
ingestion  of  food,  that  is,  an  absence  of  satiety  or  sensation  of 
fulness,  rather  than  an  abnormally  intense  hunger  sensation. 
Bulimia  may  be  temporary  or  chronic.  It  is  characterized  by  the 
fact  that  hunger  comes  on  shortly  after  eating,  and  if  it  is  not 
appeased  by  food  there  follow  headache,  weakness,  and  prostra- 
tion, just  as  in  normal  hunger  in  many  persons,  only  to  a  much 
greater  degree.  Very  small  quantities  of  food  may  appease  this 
hunger  temporarily.  This  sensation  of  hunger  may  arise  before 
the  stomach  is  empty,  although  in  many  cases  of  bulimia,  the  food 
leaves  the  stomach  more  rapidly  than  in  normal  persons  (Ewald, 
Perthes,  Sick,  Leo,  Boas).  Nicolai  concluded  that  bulimia  is  due 
to  hyperexcitability  of  the  afferent  hunger  nerves  in  the  stomach 
and  esophagus.  Ploenius  insists  that  bulimia  is  an  augmentation 
of  normal  hunger,  and  appears  only  when  the  stomach  is  empty; 
and  that  it  invariably  indicates  organic  lesions  in  the  stomach,  such 
as  local  destruction  of  the  mucosa  with  pepsin-HCl  corrosion  of 
the  deep  tissues.  According  to  Leo,  bulimia  may  occur  in  exoph- 
thalmic goitre,  in  gastric  and  duodenal  ulcer,  with  hyperacidity, 
in  chronic  gastritis,  diarrhoea,  tapeworms,  pregnancy,  excessive 
menstruation  (hemorrhage),  and  even  in  cancer  and  in  dilation  of 


HUNGER  AND  APPETITE  IN  DISEASE  263 

the  stomach.  Ewald  records  bulimia  associated  with  Addison's 
disease,  syphilis,  uterine  diseases,  and  brain  injuries  (tumors, 
emboli,  trauma).  Meyer  states  that  excessive  hunger  or  bulimia 
may  appear  in  all  types  of  neurosis. 

This  hunger  has  usually  a  very  sudden  onset,  and  is  satisfied 
or  even  turned  into  nausea  by  very  small  quantities  of  food. 
Meyer  describes  another  type  of  intense  hunger  accompanied  by 
headache,  in  which  neither  the  hunger  nor  the  headache  is  relieved 
by  eating,  and  the  ingestion  of  food  does  not  lead  to  the  sensation 
of  fulness  or  satiety.  But  in  these  patients  there  was  evidence  of 
other  cerebral  disturbances.  Meyer  argues  that  in  cases  where  the 
intense  hunger  is  satisfied  or  even  turned  to  nausea  with  a  few 
mouthfuls  of  food  we  cannot  be  dealing  with  the  mere  augmenta- 
tion of  true  hunger.  This  position  is  not  tenable.  There  may  be 
increased  excitability  of  the  inhibitory  reflexes  from  the  mouth 
and  the  gastric  mucosa,  and  hyperexcitabihty  of  the  mucosa  nerve- 
endings  would  lead  to  nausea  after  ingestion  of  even  small  quan- 
tities of  food.  Meyer  also  reports  excessive  hunger  in  certain 
persons  past  middle  life  with  tendency  to  adiposity.  Perthes 
reports  bulimia  in  persons  with  patent  pylorus.  In  some  of 
Perthes 's  patients  the  hunger  was  intense  enough  to  wake  them 
up  from  sleep  every  two  hours  during  the  night.  Boas  assumes  a 
type  of  ''idiopathic"  bulimia,  not  accompanied  by  any  other 
functional  or  organic  disturbances. 

The  excessive  hunger  in  pregnancy  is  in  all  probability  a  normal 
physiological  effect  of  the  increased  metabolism  due  to  the  growing 
fetus.  The  peculiar  fluctuation  in  the  appetite  or  desire  for  certain 
kinds  of  food  that  may  occur  in  pregnancy  involves  more  complex 
factors. 

The  bulimia  of  hypochondriacs,  and  other  types  of  neurotics, 
may  be  a  subjective  exaggeration  of  normal  hunger  impulses. 

2.  ^'Hunger  pain.'' — ^The  gastric  pains  that  appear  in  the  empty 
stomach  or  a  few  hours  after  ingestion  of  a  meal  in  persons  with 
gastric  or  duodenal  ulcers,  or  with  gall-bladder  disease  are  desig- 
nated by  Moynihan,  Hertz,  and  others  as  "hunger  pains."  In 
normal  persons  the  hunger  sensation,  if  sufficiently  strong,  is  painful. 


264        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

The  patients  with  ulcer  or  hypersecretion  describe  these  hunger 
pains  in  part  as  continuous  or  persistent,  in  part  as  variable  or 
'' gnawing,"  precisely  like  the  normal  pangs  of  hunger,  except 
that  they  are  more  intense  or  painful.  Like  the  normal  pangs  of 
hunger  the  pathological  hunger  pains  are  allayed  by  the  ingestion 
of  food.  Most  of  the  German  authors  do  not  differentiate  between 
bulimia  and  the  hunger  pains  of  gastric  and  duodenal  ulcers. 

Following  Moynihan,  many  clinicians  regard  the  hunger  pains 
in  ulcers  as  caused  by  hydrochloric  acid  stimulation  of  the  raw 
surfaces  of  the  ulcer.  In  support  of  this  view  they  cite  the  fact 
that  the  pains  are  temporarily  relieved  by  giving  alkaKes  by 
mouth.  Hertz  has  shown,  however,  that  giving  strong  acids  by 
mouth  to  ulcer  patients  does  not  cause  or  increase  the  hunger 
pains.  If  the  acid  stimulation  of  the  ulcer  gives  rise  to  these 
hunger  pains  in  ulcer  patients,  they  have  a  different  origin  from 
the  normal  hunger  pains,  as  the  latter  are  caused  by  strong  con- 
tractions of  the  stomach,  especially  of  the  fundic  and  cardiac 
regions.  The  gnawing  or  rhythmical  character  of  the  hunger  pains 
in  ulcer  cases  appears  to  the  author  to  show  that  they  are  due  to 
contractions.  If  they  were  caused  by  chemical  stimulation  of  the 
sensory  nerves  directly  we  should  expect  them  to  be  continuous. 
Hertz  has  pointed  out  additional  facts  that  support  the  mechanical 
or  contraction  origin  of  the  pains,  such  as  the  patency  of  the  pylorus, 
the  rapid  emptying  of  the  stomach,  the  hypertonicity  and  hyper- 
peristalsis  of  the  stomach,  etc.,  in  both  duodenal  and  gastric  ulcer. 
Moreover,  hypersecretion  and  hyperacidity  is  not  a  constant  factor 
in  ulcers  (Hardt),  and  the  hunger  pains  in  ulcers  may  closely 
simulate  the  gastric  pain  in  cases  of  gallstones,  appendicitis, 
gasteroptosis,  etc.,  where  there  is  no  raw  mucous  surface  to  be 
stimulated  chemically,  either  in  the  stomach  or  the  duodenum. 

Edelmann  states  that  the  gastric  digestion  peristalsis  is  directly 
dependent  on  the  acidity  of  the  gastric  juice.  But  according  to 
Eisner  the  condition  of  achyUa  gastrica  in  man  has  per  se  no 
effect  on  the  digestion  movements.  The  emptying  time  of  the 
stomach  in  achylia  may  be  normal,  less  than  normal,  or  greater 
than  normal. 


HUNGER  AND  APPETITE  IN  DISEASE  265 

The  recent  studies  on  man  by  Spencer,  Meyer,  Rehfus,  and 
Hawk  have  led  them  to  conclude  that  weak  alkalies  (podium 
bicarbonate)  in  the  stomach  hasten  the  emptying  of  the  stomach 
by  increasing  the  digestion  peristalsis  or  by  opening  the  pylorus. 
This  is  opposed  to  the  generally  accepted  view  of  the  acid  control 
of  the  pylorus,  as  developed  by  Cannon.  If  their  conclusion  is 
substantiated,  we  may  have  the  explanation  of  the  allaying  of  the 
*' hunger  pains"  in  ulcer  patients  by  oral  administration  of  alkalies. 
That  is,  the  alkalies  cause  relaxation  of  the  tetanic  spasm  of  the 
pylorus  and  antrum,  induced  reflexly  from  the  duodenum.  Glassner 
and  Kreuzfuchs  state  that  in  cases  of  gastric  ulcer  there  is  a  pro- 
longed tetanic  closure  of  the  pylorus  when  the  acid  chyme  first 
enters  the  duodenum.  This  is  a  reflex  from  the  duodenum.  The 
body  of  the  stomach  is  atonic  and  quiescent  during  this  pyloric 
spasm.  The  spasm  itself  is  felt  as  pain.  In  cases  of  duodenal 
ulcers  similar  pylorus  spasms  come  on  later  in  digestion  and  are 
likewise  felt  as  pains.  According  to  these  observers  the  hunger 
pains  in  ulcers  are  thus  due  to  pylorus  spasm,  while  Hertz  ascribes 
them  to  contractions  of  the  entire  antrum.  Pick  suggests  that  the 
pains  are  due  to  mechanical  stimulation  of  the  food  rather  than 
to  the  acid  stimulation  of  the  ulcer.  Ehrlich  protests  against  the 
view  that  '^painful  empty  stomach"  in  ulcer  patients  is  an  evidence 
of  neurosis.  According  to  Jacobi,  the  pains  of  gastric  and  duodenal 
ulcers  are  due  to  ''hypersecretion,  hyperperistalsis,  or  pressure." 

Are  the  sensations  of  "hunger  pains"  identical  with  the  normal 
pangs  of  hunger  except  for  their  greater  degree  of  painfulness  ? 
This  question  cannot  be  answered  from  the  clinical  literature,  and 
probably  will  remain  unanswered  until  the  clinical  investigator 
himself  experiences  the  pain  in  ulcer  and  allied  diseases.  These 
pains  may  lead  to  or  be  associated  with  nausea,  but  the  same  is 
true  in  normal  hunger  of  some  persons  and  in  prolonged  starvation. 
The  ''peristaltic  unrest"  of  Kussmaul  occurs  both  in  the  filled  and 
in  the  empty  stomach,  in  cases  of  pyloric  obstruction  and  in  cer- 
tain forms  of  neurosis.  The  sensations  aroused  by  this  condition 
are  said  to  be  similar  to  cramps  rather  than  to  the  pangs  of  hunger. 
The  gastralgokenosis  of  Boas  is  thought  by  this  author  to  be  due 


266        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

to  the  strong  contractions  of  the  pyloric  part  of  the  stomach  toward 
the  end  of  gastric  digestion.  Although  the  pain  disappears  on 
taking  food,  Boas  does  not  identify  it  with  true  hunger  pains.. 
The  gastralgia  in  tabes  is  generally  held  to  be  of  central  origin, 
but  so  far  as  we  know  the  tonus  and  motor  conditions  of  the  stom- 
ach have  not  been  studied  during  the  gastric  crisis  of  this  disease. 

3.  Polyphagia  and  akoria. — The  term  '^polyphagia"  is  frequently 
used  in  the  sense  of  bulimia  or  excessive  hunger.  Other  authors 
confine  it  to  excessive  ingestion  of  food  without  actual  augmenta- 
tion of  the  hunger  sensation.  In  this  latter  sense  it  implies  essen- 
tially delay  in  or  absence  of  the  sensation  of  satiety.  Nicolai 
beheved  that  polyphagia  results  from  anesthesia  of  the  stomach 
nerves  concerned  in  the  sensation  of  satiety.  But  true  akoria  or 
absence  of  satiety  occurs  mainly  in  hysteria  and  neurasthenia,  and 
has  probably  nothing  in  common  with  such  a  condition  as  the 
polyphagia  in  diabetes. 

4.  Anorexia. — The  diminution  or  absence  of  hunger  and  appetite 
in  gastero-enteritis,  in  fevers,  and  in  cachexia,  etc.,  are  in  all  prob- 
ability associated  with  atony  of  the  stomach  and  absence  of  the 
gastric  hunger  contractions.  The  evidence  for  this  view  will  be 
presented  later.  The  true  anorexia  nervosa  is  probably  of  more 
complex  origin,  involving  both  central  and  peripheral  factors. 
There  may  be  atony  and  absence  of  the  gastric  hunger  contractions 
even  in  cases  where  no  organic  lesion  in  the  stomach  can  be  demon- 
strated. In  some  cases  of  anorexia  Ewald  found  pathological 
changes  in  the  mucous  membrane  of  the  mouth,  suggesting  disorders 
of  the  sense  of  taste.  • 

When  the  anorexia  is  very  marked  it  may  be  accompanied  by 
nausea,  at  least  at  the  sight,  smell,  or,  taste  of  food,  or  an  actual 
fear  of  food  and  eating  (sitophobia) .  Under  other  conditions  a 
mild  nausea  may  be  present  synchronously  with  practically  normal 
hunger  and  appetite  (Boas).  We  have  seen  that  this  may  occur 
in  normal  individuals  in  prolonged  starvation.  Nervous  anorexia 
is  more  common  in  women  than  in  men.  Vertes  takes  the  position 
that  most  of  the  disturbances  of  hunger  and  appetite  that  appear 
in  pregnancy,  ovarian  diseases,  menstrual  disorders,  etc.,  are  in 


HUNGER  AND  APPETITE  IN  DISEASE  267 

reality  independent  of  the  latter,  while  in  a  few  cases,  they  are 
reflex  neuroses.  The  actual  state  of  the  gastric  hunger  mechanism 
in  these  conditions  is  not  known. 

5.  Parorexia. — ^This  term  is  used  to  designate  various  types  of 
abnormal,  perverted,  or  depraved  appetite.  These  conditions  refer 
exclusively  to  appetite,  rather  than  to  hunger,  at  least  it  has  not 
been  shown  that  hunger  is  at  all  involved.  The  least  abnormal 
condition  appears  to  be  the  malacia,  or  desire  for  highly  spiced  or 
acid  foods  that  are  sometimes  seen  in  chlorotic  girls  and  in  preg- 
nant women.  Another  type — pica — ^is  the  appetite  for  substances 
that  are  not  food,  such  as  clay,  chalk,  or  earth.  These  materials 
are  eaten,  especially  by  children,  because  they  like  the  taste  of 
them.  This  is  probably  a  bad  habit,  rather  than  an  indication  of 
seriously  perverted  mental  processes.  Most  of  our  domestic  ani- 
mals, even  those  that  appear  perfectly  healthy,  eat  earth  at  times, 
aside  from  the  quantity  of  earth  consumed  with  their  ordinary 
food  and  drink.  And  even  with  the  best  of  care  in  the  way  of  food 
hygiene,  we  all  consume  more  or  less  earth,  dirt,  stable  manure, 
etc.,  with  our  food.  To  the  mind  of  the  average  adult  earth  has 
become  synonymous  with  dirt  or  filth,  hence  we  abhor  taking  it 
into  the  mouth,  just  as  the  average  person  loathes  snakes.  The 
child,  not  having  formed  these  associations,  puts  sand,  chalk,  or 
earth  into  his  mouth  from  general  curiosity  or  in  the  spirit  of  play, 
and  may  or  may  not  like  the  new  experience.  If  he  likes  it,  he  will 
repeat  it  until  he  learns  the  usual  social  canons.  Clay  eating  is  on 
a  par  with  gum  chewing  and  tobacco  chewing,  and  is  certainly  less 
injurious  and  nasty  than  the  latter  habit. 

6.  Allotriophagia,  or  desire  for  disgusting  and  offensive  sub- 
tances,  such  as  human  excreta,  body  lice,  etc.,  is  practically  confined 
to  insane  individuals,  or  extreme  degenerates.  It  is  likely  that  the 
habit  is  reached  via  the  route  of  sexual  depravity,  at  least  in  many 
cases.  In  persons  with  the  ordinary  idea-associations  lost  or 
suppressed,  tolerance  and  even  liking  for  any  kind  of  taste  and 
odor  can  apparently  be  cultivated.  We  all  know  that  animal 
excreta  are  regularly  ingested  by  many  normal  animals,  though 
most  of  them  pass  by  those  of  their  own  species. 


268        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

III.      CONDITION   OF   THE   GASTRIC  HUNGER  MECHANISM   IN 
DISEASE    OF   EXPERIMENTAL  ANIMALS 

1.  Pancreatic  diabetes. — Experimental  pancreatic  diabetes  in 
animals  is  accompanied  by  the  excessive  hunger  or  polyphagia  of 
diabetes  mehtus  in  man.  Dr.  Luckhardt  studied  the  gastric  hunger 
contractions  in  two  dogs  during  the  entire  course  of  fatal  pancreatic 
diabetes.  With  good  care  dogs  live  from  4  to  6  weeks  after  complete 
pancreatectomy,  showing  progressive  emaciation  despite  their  exces- 
sive intake  of  food.  In  both  the  diabetic  dogs  the  gastric  tonus 
and  hunger  contractions  were  more  continuous  and  vigorous  than 
in  normal  dogs  or  in  the  same  dogs  before  they  became  diabetic. 
This  augmentation  of  the  gastric  hunger  contractions  persisted  up 
till  within  24  hours  of  the  death  of  the  animals,  despite  the  progres- 
sive and  finally  extreme  emaciation  and  weakness.  The  increased 
food  consumption  of  the  dogs  thus  ran  parallel  with  the  greater 
vigor  of  the  peripheral  hunger  mechanism.  And  there  can  be  little 
doubt  that  the  dogs  felt  greater  hunger  and  consumed  more  food 
because  of  the  greater  vigor  of  the  gastric  hunger  contractions. 

The  cause  of  this  augmented  contraction  of  the  empty  stomach 
in  diabetes  is  still  an  open  question.  It  is  evidently  due,  at  least 
in  part,  to  some  change  in  the  blood,  for  transfusion  of  diabetic 
blood  into  normal  dogs  stimulates  the  hunger  contractions  in  the 
latter.  Allen  states  that  when  partial  diabetes  in  man  is  controlled 
by  means  of  temporary  starvation  and  dieting,  so  that  the  urine 
becomes  free  from  sugar  and  the  acidosis  disappears,  the  polyphagia 
of  the  diabetic  patient  also  disappears,  but  we  do  not  know  whether 
the  latter  is  due  to  a  return  of  the  gastric  hunger  mechanism  to  the 
normal  state  of  activity. 

2.  Polyphagia  and  augmented  gastric  hunger  contractions  in  dogs 
with  mange. — A  number  of  dogs  kept  in  the  laboratory  for  long 
periods  in  the  course  of  certain  lines  of  investigation  became 
afflicted  with  mange.  Dr.  Luckhardt  observed  that  these  mangy 
dogs  consumed  a  much  greater  amount  of  food  than  they  did  before 
contracting  or  after  being  cured  of  the  disease.  It  was  also  noted 
that  a  dog  with  mange  is  more  susceptible  to  cold  than  normal 
dogs,  as  shown  by  their  almost  constant  shivering,  even  in  a  room 


Fig.  30. — Records  of  the  gastric  hunger  contractions  of  a  dog  before  and  during 
fatal  pancreatic  diabetes  (Luckhardt).  Bottom  of  tracings  +0  pressure  of  bromoform. 
A ,  type  II  contractions  indicating  moderate  hunger  in  dog  before  rendered  diabetic. 
Four-fifths  original  size.  5,  culmination  of  a  tetany  period  in  the  diabetic  animal  last- 
ing about  20  minutes.  Smaller  tetany  periods  are  likewise  shown.  Throughout,  a 
type  III  rhythm  on  a  high  tonus.  Two-thirds  original  size.  C,  tracing  obtained  from 
the  empty  stomach  of  a  diabetic  dog  less  than  2  days  before  death.  Throughout, 
type  III  contractions  on  a  high  tonus.  Dog  too  weak  to  walk.  Ate  105  gm.  meat — 
the  last  meal  before  death,  which  followed  2  days  later.    Two-thirds  original  size. 


2  70        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

with  temperature  ranging  from  55°  to  65°  F.  This  is  probably  due 
to  the  loss  of  hair,  and  to  interference  with  the  normal  vaso- 
constrictor   reflexes    of    the    skin    by    the    persistent    cutaneous 


Fig.  31. — Tracing  from  empty  stomach  of  dog  while  normal  (A),  and  after 
developing  severe  mange  (B);  showing  abnormally  intense  gastric  hunger  parallel 
with  the  mange  and  the  polyphagia  (Luckhardt) . 


hyperemia.    These  conditions  must  involve  an  abnormal  heat  loss 
from  the  skin. 

The  gastric  tonus  and  hunger  contractions  were  studied  in  a 
number  of  these  mangy  and  polyphagic  dogs,  in  order  to  determine 
whether  the  greater  hunger  was  due  to  greater  gastric  hunger 


HUNGER  AND  APPETITE  IN  DISEASE  271 

contractions.  This  proved  to  be  the  case.  A  dog  with  extensive 
mange  but  otherwise  healthy  exhibits  abnormally  great  gastric 
tonus  and  hunger  contractions.  The  latter  tend  to  become  tetanic, 
and  when  this  is  not  the  case,  the  individual  contractions  are  abnor- 
mally strong.  The  polyphagia  of  the  mangy  dogs  is  therefore  due  to 
the  greater  vigor  of  the  gastric  hunger  mechanism.  The  stronger 
gastric  contractions  are  probably  brought  about  indirectly  through 
,  increase  in  muscular  metaboHsm  as  a  result  of  the  too  great  loss  of 
heat  from  the  skin,  in  other  words,  the  same  effects  as  we  found  on 
exposing  normal  men  and  animals  to  great  and  prolonged  cold. 

3.  Hunger  and  appetite  in  cases  of  alcoholic  gastritis  in  dogs. — 
Dr.  Luckhardt  found  that  whiskey  or  strong  alcohol  introduced 
directly  into  the  empty  stomach  of  dogs  in  sufficient  amount  to 
induce  marked  narcosis  abolishes  the  tonus  and  hunger  contrac- 
tions of  the  stomach  for  24  to  36  hours.  During  this  period  the 
animal  refuses  food  and  may  vomit  at  times.  After  36  to  48  hours 
the  hunger  contractions  gradually  return  and  may  at  times  even 
approach  the  condition  of  incomplete  tetanus.  The  dog  shows 
interest  in  food,  but  may  eat  only  a  mouthful.  Occasional  vomiting 
still  continues.  Evidently  the  gastric  mucosa  continues  hyper- 
sensitive for  a  much  longer  time  than  the  period  of  motor  paralysis 
of  the  stomach,  so  that  ingestion  of  food  induces  or  increases 
nausea  and  gastric  distress,  despite  the  fact  that  hunger  contractions 
and  hunger  sensations  are  present.  In  other  words,  the  dog  experi- 
ences hunger  and  nausea  at  the  same  time.  That  the  dog  actually 
feels  the  contractions  of  the  empty  stomach  as  hunger  seems  to  be 
shown  by  the  fact  that  he  walks  up  to  the  food  from  time  to  time, 
sniffs  at  the  food,  and  may  even  start  to  eat  a  little.  At  the  end 
of  several  days,  vomiting  disappears  entirely  and  the  dog  resumes 
normal  feeding. 

The  interesting  point  in  these  observations  is  the  recovery  of 
strong  gastric  hunger  contractions  a  considerable  time  before  the 
dog  starts  normal  feeding.  We  think  the  disinclination  to  eat, 
despite  moderately  strong  hunger,  is  due  to  nausea  induced  from 
the  hyperexci table  gastric  mucosa.  After-effects  of  alcohol  on  the 
brain  may  also  play  a  role. 


272        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 


D 


Fig.  32. — Tracings  from  empty  stomach  of  dog  showing  effect  of  alcoholic 
gastritis  on  the  hunger  mechanism  (Luckhardt).  A,  gastric  hunger  contractions  of 
dog  before  inducing  alcoholic  gastritis.  B,  tracing  showing  atonic  stomach  of  dog  24 
hours  after  excessive  administration  of  alcohol  by  stomach  tube.  Dog  drinks  water 
and  vomits  but  refuses  food.  C  and  D,  moderate  gastric  hunger  contractions  of  dog 
3  and  4  days  after  the  alcoholic  debauch.  Dog  ate  a  little,  and  vomited  frequently, 
evidently  being  nauseated  and  feeling  some  hunger  at  the  same  time.  E,  vigorous 
hunger  contractions  8  days  after  inducing  the  gastritis;  dog  normal  and  eating 
greedily. 


HUNGER  AND  APPETITE  IN  DISEASE  273 

4.  Paralysis  of  the  gastric  hunger  mechanism  in  pneumonia, 
distemper,  and  general  peritonitis. — Dogs  with  well-advanced  pneu- 
monia or  distemper  refuse  all  food.  Such  dogs  show  complete  atony 
and  absence  of  gastric  hunger  contractions.  This  is  likely  the 
condition  of  the  empty  stomach  in  all  acute  infections  of  sufficient 
severity.  The  mechanism  of  the  failure  of  the  hunger  contractions 
in  these  acute  infections  is  not  known.  The  bacterial  toxins  may 
depress  the  motor  mechanism  of  the  stomach  directly,  lower  the 
vagus  tonus,  augment  inhibitory  reflexes,  or  induce  excessive  secre- 
tion of  epinephrin.  The  elevated  temperature  may  also  play  a 
role.  Cannon  observed  that  infections  also  depress  the  digestion 
peristalsis  of  the  stomach  and  intestines  in  cats. 

5.  Depression  of  the  gastric  hunger  contractions  in  parathyroid 
tetany. — Animals  in  parathyroid  tetany  show  decrease  or  absence 
of  desire  for  food  in  direct  proportion  to  the  severity  of  the  tetany 
and  cachexia  symptoms.  Is  this  refusal  of  food  due  to  absence  of 
the  gastric  hunger  contractions  ? 

Our  observations  were  made  on  three  dogs.  The  dogs  were 
observed  every  third  day  for  two  weeks,  so  as  to  secure  the  average 
normal  gastric  tonus  and  hunger  contractions  before  extirpation 
of  the  parathyroid.  All  three  dogs  ran  a  typical  course  of  tetany 
of  varying  severity  from  day  to  day.  Dog  I  died  in  tetany  on  the 
sixth  day  after  the  operation;  Dogs  II  and  III  died  in  depression 
on  the  eighth  and  tenth  days  respectively.  The  results  were 
practically  the  same  in  the  three  dogs.  In  this  tetany  there  is 
depression  of  the  tonus  and  contraction  of  the  empty  stomach 
parallel  with  the  severity  of  the  tetany,  so  that  during  extreme 
tetany  the  stomach  is  practically  atonic,  and  tonus  contractions 
and  hunger  contractions  are  completely  absent.  The  milder  stages 
of  the  tetany  (hyperexcitability  of  the  motor  nerves,  slight  tremors, 
twitchings,  and  some  salivation)  may  coexist  with  considerable 
gastric  tonus  and  hunger  contractions,  but  the  hunger  contractions 
are  always  slower  and  weaker  than  normal. 

It  is  well  known  that  the  course  of  parathyroid  tetany,  especially 
in  dogs,  is  usually  more  or  less  periodic,  the  animal  recovering 
spontaneously  for  periods  varying  from  a  few  hours  to  a  day  or 


274        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

.  more  between  the  tetany  attacks.  Dog  II  showed  two  such  periods 
of  spontaneous  recovery  of  34  and  20  hours'  duration.  During 
these  periods  the  gastric  hunger  contractions  and  the  gastric  tonus 
also  returned  to  approximately  normal  conditions,  the  dog  at  the 
same  time  taking  normal  interest  in  food. 

The  relation  of  these  depressions  of  hunger  and  appetite  to  the 
gastric  hunger  contraction  is,  nevertheless,  not  a  direct  one.  Dur- 
ing the  mild  stages  of  tetany  the  failure  of  hunger  and  appetite  is 
usually  much  greater  than  one  would  expect  on  the  basis  of  the 
degree  of  depression  of  the  hunger  contractions.  In  strong  tetany 
there  are  no  gastric  hunger  contractions  and  the  dogs  refuse  food, 
but  the  dog  may  refuse  food  even  though  fairly  strong  hunger 
contractions  are  present  in  mild  tetany,  or  if  he  does  eat  the  amount 
of  food  consumed  is  very  small.  It  is  therefore  clear  that  the 
depression  of  hunger  and  appetite  in  tetany  cannot  be  accounted 
for  solely  on  the  basis  of  depression  of  gastric  hunger  contractions, 
although  this  is  unquestionably  one  of  the  factors.  But  we  must 
also  take  into  account  either  a  change  in  the  central  nervous  system, 
or  a  change  in  the  character  of  the  nervous  impulses  from  the 
stomach  and  other  proprioceptor  systems. 

The  condition  of  parathyroid  tetany,  so  far  as  it  influences  the 
stomach  motor  activities,  depresses  both  the  digestion  movements 
of  the  filled  and  the  hunger  contractions  of  the  empty  stomach, 
but  the  movements  of  digestion  show  less  depression  than  do  the 
hunger  contractions.  Thus  moderately  strong  tetany  may  leave 
the  gastric  digestion  movements  practically  normal  but  completely 
inhibit  the  hunger  contractions  of  the  empty  stomach.  The  tetany 
condition  does  not  lead  to  increased  motor  activity,  either  in  the 
empty  or  the  filled  stomach. 

The  cause  of  this  depression  of  the  gastric  motor  activities  in 
parathyroid  tetany  is  not  determined.  In  the  case  of  the  digestion 
movements  it  was  shown  not  to  be  due  to  splanchnic  inhibition. 
This  test  has  not  been  made  in  the  case  of  the  hunger  movements. 
But  one  factor  in  the  depression  or  complete  inhibition  of  the  hun- 
ger, contraction  in  tetany  is  the  increased  excitabiHty  of  the  nerve- 
endings  in  the  gastric  mucosa.    Vomiting  is  a  tetany  symptom  in 


HUNGER  AND  APPETITE  IN  DISEASE  275 

dogs.  And  dogs  in  tetany  frequently  vomit  with  nothing  in  the 
stomach  but  bile  and  saliva.  In  such  dogs  water  at  body  tempera- 
ture introduced  into  the  stomach  through  a  fistula  in  the  fundus 
causes  vomiting.  The  presence  of  a  delicate  rubber  balloon  in  the 
stomach  or  the  sHght  inflation  of  the  balloon  causes  vomiting. 
This  never  occurs  in  normal  dogs.  The  stimulation  of  the  nerve- 
endings  in  the  gastric  mucosa  in  normal  animals  (man  and  dog) 
causes  inhibition  of  the  gastric  hunger  contractions  through  weak 
and  long  reflexes.  In  parathyroid  tetany  these  nerve-endings  in  the 
mucosa  become  so  hypersensitive  that  they  are  intensely  stimulated 
by  saliva,  water,  bile,  and  gastric  juice.  But  in  addition  to  these 
inhibitory  reflexes  from  the  gastric  mucosa  we  probably  also  have  a 
direct  depression  of  the  automatic  tissue  in  the  stomach,  for  it  is  not 
likely  that  the  inhibitory  reflexes,  even  though  very  strong,  could 
maintain  the  sustained  extreme  depression  seen  in  strong  tetany. 

By  way  of  summary,  we  conclude  that  parathyroid  tetany  in 
dogs  does  not  lead  to  increased  tonus  or  contractions  of  the  empty 
stomach,  but  to  depression  of  the  tonus  and  the  hunger  contractions. 
The  degree  of  the  depression  of  the  motor  activities  of  the  empty 
stomach  is  on  the  whole  parallel  with  the  severity  of  the  tetany 
symptoms,  and  more  marked  than  the  depression  of  the  gastric 
movements  of  the  digestion.  The  hyperexcitability  of  the  nerve- 
endings  in  the  gastric  mucosa  is  a  factor  in  this  depression.  The 
stimulation  of  these  nerve-endings  leads,  through  local  and  long 
reflexes,  to  inhibition  of  the  tonus  and  the  hunger  movements. 
There  is  probably  also  a  direct  depression  of  the  automatic  tissue 
in  the  stomach  through  changes  in  the  blood.  The  diminution  or 
lack  of  appetite  for  food  in  animals  in  tetany  is  on  the  whole  greater 
than  would  be  expected  on  the  basis  of  the  degree  of  the  depression 
of  the  gastric  hunger  contractions.  The  cause  of  the  lack  of  hunger 
and  appetite  in  tetany  is  therefore  complex.  It  is  due  in  part  to 
the  depression  of  the  gastric  hunger  contractions.  Other  factors 
are  the  change  in  the  brain,  and  in  the  character  of  the  other 
afferent  nervous  impulses. 

6.  Increase  in  gastric  tonus  and  hunger  contractions  in  dogs  after 
partial  occlusion  of  the  pylorus. — It  is  well  known  that  pyloric 


276       CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

obstruction  in  man  leads  to  various  disturbances  of  the  gastric- 
digestion  movements,  as  well  as  to  disturbances  of  the  hunger 
sensation.  In  order  to  determine  whether  any  of  the  latter  dis- 
turbances, and  particularly  the  stronger  gastric  pains  that  are  so 
frequently  in  evidence  in  pyloric  obstruction,  are  due  to  changes 
in  the  motihty  of  the  empty  stomach,  the  hunger  contractions  of 
the  empty  stomach  after  partial  occlusion  of  the  pylorus  were 
studied  in  two  dogs  by  Dr.  Elsesser. 

The  pyloric  obstruction  was  made  in  the  following  manner. 
The  serosa  extending  across  the  pyloric  sphincter  about  f  cm.  by 
I J  cm.  was  scarified,  care  being  taken  to  avoid  injury  to  the  larger 
blood  vessels  of  that  region.  Two  rows  of  stitches  running  parallel 
to  the  long  axis  of  the  bowel  were  made,  the  second  folding  in  the 
first,  thus  bringing  the  two  scarified  surfaces  together  and  at  the  same 
time  partially  occluding  the  pyloric  lumen.  The  method  has  these 
advantages,  that  some  pyloric  obstruction  is  sure  to  be  produced 
which  will  be  firmly  maintained  by  adhesions  forming  between  the 
two  raw  surfaces.  Furthermore,  complete  occlusion  and  loss  of  the 
animal  is  avoided,  a  termination  frequently  attendant  upon  placing 
ligatures  around  the  pylorus.  After  the  animal  had  recovered  suffi- 
ciently from  the  effect  of  the  operation — sc  matter  of  several  days — 
records  of  the  gastric  hunger  contractions  were  made  dupHcating  the 
normal  ones,  both  as  to  conditions  and  periods  of  time.  On  one  dog, 
which  we  may  designate  as  Dog  A,  a  second  operation  similar  to  the 
first  was  performed  and  a  second  series  of  tracings  was  obtained. 

Dog  A  remained  very  well  and  active  and  was  killed  35  days 
after  the  first  and  14  days  after  the  second  operation.  At  autopsy 
the  pylorus  presented  a  lumen  constricted  by  a  hard,  tough  mass 
of  granulation  tissue,  the  seat  of  the  scarification  and  stitching. 
The  stomach  was  not  distended,  but  showed  some  hypertrophy. 
The  gastric  mucosa  lay  in  deep  folds.  Dog  B  became  somewhat 
emaciated  after  stenosis,  evinced  a  hypersensitivity  of  the  gastric 
mucosa  by  occasional  vomiting  of  the  balloon  while  records  were 
being  made.  At  autopsy  the  pylorus  was  constricted,  so  that  the 
stomach  contents  would  be  forced  through  it  only  with  difficulty. 
The  stomach  itself  was  considerably  dilated. 


HUNGER  AND  APPETITE  IN  DISEASE 


277 


Both  dogs  gave  evidence  of  delayed  emptying  of  the  stomach 
after  the  stenosis,  in  that  food  remnants  were  frequently  found  in 
the  stomach  more  than  24  hours  after  feeding. 


Fig.  33. — Tracings  showing  contractions  of  the  stomach  of  dog  A.  Dog  normal; 
tracing,  taken  48  hours  after  feeding,  represents  height  of  a  period  of  hunger  contrac- 
tions; B,  same  dog  as  in  tracing  A,  42  hours  after  feeding,  30  days  after  production 
of  partial  stenosis  of  the  pylorus,  showing  typical  hypertonus  and  tetany  periods  of 
the  empty  stomach.    Chloroform  manometer.    Time,  15  minutes  (Elsesser). 


2  78        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

After  recovery  from  the  operations  the  empty  stomachs  of  these 
two  dogs  showed  more  continuous  and  on  the  whole  stronger 
hunger  contractions  than  before  the  operation,  with  a  tendency 
for  the  contraction  to  pass  into  long  periods  of  incomplete  tetanus. 
It  is  thus  clear  that  partial  stenosis  of  the  pylorus  induces  a  hyper- 
motility  in  the  stomach,  irrespective  of  the  presence  of  food  in  the 
stomach  cavity.  The  hypermotility  of  the  stomach  during  gastric 
digestion  may  be  a  temporary  condition  induced  by  the  presence 
of  the  food  and  retardation  of  its  passage  through  the  pylorus,  a 
condition  similar  to  that  of  the  small  intestine  above  a  region  of 
obstruction.  The  fact  that  the  hypermotility  is  present  even  in 
the  empty  stomach  seems  to  show  that  the  motor  changes  following 
mere  mechanical  obstruction  of  the  pylorus  are  more  fundamental 
and  permanent. 

The  mechanism  of  this  increased  motility  can  as  yet  only  be 
conjectured.  Bacterial  toxins  from  local  foci  of  infection  are 
excluded  in  these  experiments,  as  the  partial  stenosis  was  produced 
aseptically  in  animals  with  normal  stomachs  and  without  sub 
sequent  infection.  We  may  be  dealing  with  nervous  reflexes  from 
the  pylorus  involving  the  entire  stomach. 

By  way  of  summary,  we  conclude  that  partial  pyloric  stenosis 
in  dogs  produces  hypertonicity,  hypermotihty,  and  hyperperistalsis 
of  the  empty  stomach,  even  if  of  but  a  few  days'  or  weeks'  duration. 
These  motor  phenomena  are  similar  to  those  seen  in  the  filled 
stomach  in  man  with  partial  obstruction  of  the  pylorus.  The  same 
conditions  which  lead  to  hyperperistalsis,  etc.,  during  digestion, 
led  at  the  same  time  to  increased  motility  of  the  empty  stomach. 
In  other  words,  partial  pyloric  stenosis  appears  to  produce  a  neuro- 
muscular hyperactivity,  independent  of  the  presence  of  food  in 
the  stomach. 

IV.      EXPERIMENTAL   INVESTIGATION   OF   THE   HUNGER 
MECHANISM   IN  DISEASE    OF   MAN 

I.  Absence  of  gastric  hunger  contractions  in  gastritis,  tonsillitis, 
influenza,  and  ^'colds.^^ — During  the  four  years  that  Mr.  V.,  the 
gastric-fistula  case,  has  been  under  observation  in  our  laboratory 


HUNGER  AND  APPETITE  IN  DISEASE  279 

he  has  had  a  few  attacks  of  mild  gastritis,  in  three  cases  associated 
with  nose  and  throat  colds,  with  some  temperature.  During  these 
attacks  the  empty  stomach  remained  somewhat  atonic  with  com- 
plete absence  of  the  hunger  contractions.  Mr.  V.  felt  no  hunger 
and  had  little  or  no  desire  to  eat.  In  fact,  putting  food  in  the 
stomach  in  these  conditions  sometimes  produced  nausea.  The 
absence  of  hunger  and  depression  of  the  appetite  thus  ran  parallel 
with  the  impairment  of  the  gastric  hunger  mechanism. 

Luckhardt  and  Hamburger  have  reported  gastric  atony  and 
absence  of  hunger  contractions  in  a  case  of  acute  gastritis  brought 
on  by  dietary  indiscretion.  The  author  has  taken  records  on  him- 
self in  one  mild  attack  of  gastritis,  lasting  three  days,  two  attacks 
of  ^'cold"  and  tonsillitis,  one  of  which  was  complicated  with  painful 
antrum  infection.  During  the  gastritis  the  empty  stomach  showed 
no  hunger  contraction.  The  tonsillitis,  ''colds,"  and  antrum 
infection  did  not  completely  abolish  the  hunger  contractions,  except 
when  sufficiently  severe  to  induce  elevation  of  the  body  temperature 
to  101°  or  102°  F.  Again,  the  depression  or  absence  of  the  feeling 
of  hunger  ran  parallel  with  the  degree  of  depression  of  the  gastric 
hunger  contractions.  But  even  when  no  hunger  was  experi- 
enced, the  sight  of  palatable  food  was  capable  of  inducing  some 
appetite. 

2.  Hunger  in  diabetes  mellitus. — Dr.  Luckhardt  studied  the 
gastric  hunger  contractions  of  a  man  twenty-nine  years  of  age,  in 
the  last  stage  of  diabetes.  The  empty  stomach  showed  abnormally 
strong  hunger  contractions  till  within  a  few  days  of  death  in  coma, 
the  patient  at  the  same  time  complaining  of  great  hunger.  This 
seems  to  show  that  in  clinical  diabetes  there  is  an  increased  activity 
of  the  gastric  hunger  mechanism  similar  to  that  demonstrated 
in  pancreatic  diabetes  in  dogs.  But  more  observations  are  needed 
on  clinical  diabetes  before  this  relation  can  be  accepted  or 
demonstrated. 

3.  Gastric  hunger  contractions  in  a  case  of  gastric  cancer. — The 
subject  was  an  old  man,  considerably  emaciated,  but  with  no 
serious  obstruction  at  the  pylorus.  His  hunger  and  appetite  were 
good  and  his  gastric  hunger  contractions  normal.    This  observation 


28o       CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 


Fig.  34. — A,  normal  hunger  contractions  of  the  empty  stomach  of  a  neurasthenic 
man.  The  contractions  gave  rise  to  epigastric  pain,  not  hunger  pangs.  B,  tetanic 
contractions  of  the  empty  stomach  of  a  man  with  carcinoma  of  the  stomach  and  par- 
tial pyloric  obstruction.  The  contractions  caused  epigastric  distress,  rather  than 
true  hunger.  C,  vigorous  hunger  contractions  of  the  empty  stomach  of  a  diabetic 
man,  5  days  before  death  in  diabetic  coma,  showing  vigorous  hunger  contractions 
associated  with  the  diabetic  polyphagia  (Luckhardt  and  Hamburger) . 


HUNGER  AND  APPETITE  IN  DISEASE  281 

of  Luckhardt  and  Hamburger  is  in  line  with  the  fact  that  patients 
with  cancer  of  the  stomach  may  continue  to  feel  hunger  when 
the  tumor  growth  is  so  advanced  that  feeding  by  mouth  becomes 
impossible. 

4.  Excessive  pain  produced  by  normal  gastric  hunger  contractions 
in  neurasthenics. — Dr.  Luckhardt  reports  a  case  of  a  man  who 
sought  hospital  treatment  for  a  dull  ache  or  epigastric  pain  which 
came  on  whenever  the  stomach  was  empty.  This  pain  or  ache 
proved  to  be  due  to  the  hunger  contractions  of  the  empty  stomach, 
the  latter  not  being  stronger  than  those  observed  in  normal  indi- 
viduals. The  patient  believed  that  the  observation  of  his  stomach 
by  the  balloon  method  was  a  method  of  treatment.  The  patient 
stated  after  a  few  days  that  the  pain  had  ceased  entirely,  although 
the  gastric  hunger  contractions  continued  normal,  and  he  left  the 
hospital  very  grateful  for  what  had  been  done  for  him.  There  was 
no  evidence  of  organic  lesion  in  the  stomach.  This  case  presents 
either  a  temporary  neurosis  (hyperexcitability)  of  the  gastric  hun- 
ger nerves  so  that  the  normal  contractions  actually  give  rise  to 
abnormally  strong  impulses,  or  else  the  normal  impulses  from  the 
stomach  become  exaggerated  in  consciousness  through  perverted 
attention. 

The  author  studied  the  gastric  hunger  contractions  of  a  similar 
case,  a  young  farmer  seeking  medical  aid  for  excessive  epigastric 
pain,  and  some  feeling  of  weakness  and  depression.  No  organic 
lesions  could  be  detected.  The  gastric  hunger  contractions  were 
strong,  the  periods  ending  in  incomplete  tetanus,  but  equally  strong 
hunger  tonus  and  contractions  have  been  seen  in  normal  individuals 
of  his  age  and  occupation.  Yet  the  tonus  and  contractions  were  to 
him  sufficiently  painful  to  seek  medical  aid  repeatedly,  but  no 
treatment  appeared  to  give  permanent  relief. 

5.  Cause  of  the  ^^ hunger  pains'''  in  cases  of  gastric  and  duodenal 
ulcers. — Hamburger,  Ginsburg,  and  Tumpowsky  found  that  the 
'' gnawing"  hunger  pains  in  duodenal  and  gastric  ulcers  are  caused 
by  the  hunger  contractions  of  the  empty  or  partly  empty  stomach. 
These  contractions  are,  on  the  whole,  not  stronger  than  those  of 
healthy  persons  in  hunger,  yet  they  are  felt  as  much  more  painful 


282        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 


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HUNGER  AND  APPETITE  IN  DISEASE  283 

than  the  normal  hunger  pangs.  This  may  be  due  to  hyperexcita- 
biUty  of  the  sensory  nerve-fibers  in  the  stomach.  These  patients 
usually  feel  a  more  or  less  steady  and  dull  gastric  pain  besides  the 
gnawing  or  intermittent  pains  associated  with  the  rhythmical 
contractions.  The  cause  of  the  continuous  but  less  sharp  pain  is 
probably  to  be  sought  in  the  steady  and  strong  tonus  contractions 
of  some  region  of  the  stomach  or  duodenum.  This  steady  but  dull 
gastric  pain  in  ulcer  patients  is  thus  similar  in  origin  to  that  felt 
by  some  people  in  prolonged  starvation. 

If  the  theory  of  infectious  origin  of  ulcers  indicated  by  the  work 
of  Rosenow  is  applicable  in  all  cases,  the  hyperexcitability  of  the 
gastric  sensory  nerves  in  ulcer  is  probably  due  to  the  local  inflam- 
matory processes.  Even  in  ulcers  of  traumatic  origin  (chemical, 
mechanical)  secondary  infection  probably  takes  place,  so  that  even 
in  such  cases  we  have  local  inflammation. 

6.  Cause  of  gastric  pain  in  diseases  of  the  gall  bladder. — ^We  do 
not  refer  to  the  pain  definitely  due  to  the  mechanical  stimulation 
of  the  gall  bladder  or  the  bile  duct  by  biliary  calculi,  but  to  the 
epigastric  pains  that  come  on  a  certain  length  of  time  after  a  meal, 
and  closely  resemble  the  hunger  pains  of  ulcer.  We  know  that 
the  rhythmical  contractions  of  the  gall  bladder  are  greatly  aug- 
mented during  gastric  digestion,  probably  through  reflex  stimu- 
lation of  acid  chyme  in  the  duodenum.  In  this  manner,  pain  from 
the  gall  bladder  itself  may  be  augmented  parallel  with  gastric 
digestion  peristalsis  especially  in  cases  of  hypersecretion. 

Ginsburg  and  Tumpowsky  studied  the  epigastric  pain  in  one 
patient  with  gall-bladder  infection,  as  determined  by  clinical  diag- 
nosis. Gastric  and  duodenal  ulcers  were  excluded.  In  this  patient 
the  pain  ran  absolutely  parallel  with  the  strong  hunger  contractions 
of  the  empty  or  nearly  empty  stomach.  The  hunger  contractions 
were  stronger  than  usual  for  a  man  of  the  patient's  age.  We  can- 
not be  sure  that  the  gastric  contractions  were  the  only  cause  of 
the  pains;  there  may  be  strong  contractions  of  the  gall  bladder 
parallel  with  the  stomach  contractions. 

In  this  patient,  too,  the  epigastric  pain  appeared  greater  than 
warranted  by  the  strength  of  the  gastric  contractions.    Evidently 


284        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

gall-bladder  infections  may  lead  to  hyperexcitability  of  the  sensory 
nerve-fibers  of  the  stomach  and  duodenum,  possibly  from  the 
spread  of  bacterial  toxins  along  the  branches  of  the  vagi  nerves. 

7.  Hunger  contractions  of  the  empty  stomach  in  infants  with 
pyloro spasm  and  congenital  pyloric  5/ew(?5w.— Pylorospasm  has  been 
ascribed  to  a  great  variety  of  causes,  including  primary  neurosis 
of  the  local  motor  mechanism.  The  hyperperistalsis  of  the  filled 
stomach  usually  associated  with  spasms  of  the  pylorus  may  be  a 
temporary  condition  due  to  the  presence  of  food  in  the  stomach. 
On  the  other  hand,  if  pylorospasm  is  simply  an  expression  of  pri- 
mary hypermotility  of  the  entire  stomach,  this  condition  of  hyper- 
tonus  and  hypermotility  should  also  be  in  evidence  when  the 
stomach  is  empty.  A  study  of  the  motor  conditions  of  the  empty 
stomach  may  thus  aid  in  determining  some  of  the  factors  involved 
in  hypercontractility  of  the  pyloric  sphincter.  In  infants  '^  rumina- 
tion" is  probably  always  secondary  to  chronic  vomiting,  which  in 
turn  may  or  may  not  be  associated  with  pylorospasm.  If  the 
vomiting  is  due  to  gastric  hypertonicity  and  hypermotility,  these 
conditions  should  also  be  present  in  the  empty  stomach,  with  or 
without  the  involvement  of  the  pylorus. 

We  have  studied  the  motor  conditions  of  the  empty  stomach  in 
two  infants,  one  with  congenital  pyloric  stenosis,  and  one  with 
pylorospasm,  chronic  vomiting,  and  rumination. 

Case  I :  Infant  three  months  old;  chronic  vomiting  and  gradual 
loss  of  weight.  Congenital  pyloric  stenosis.  Gastro-enterostomy 
was  made.  The  pylorus  was  found  contracted,  and  somewhat 
edematous  and  anemic.  Before  the  operation,  record  of  the  tonus 
and  contractions  of  the  empty  stomach  was  made  by  the  balloon 
method  as  appHed  to  infants.  The  strength  of  the  contractions  was 
markedly  greater  than  in  normal  infants.  The  duration  of  the 
periods  of  contraction  was  also  greater.  This  indicates  a  greater 
than  normal  gastric  tonus.  There  was  no  indication  of  prolongjed 
tetanic  contractions. 

Case  2:  Infant  five  months  old;  chronic  vomiting  ("rumina- 
tion"). Practically  stationary  body  weight.  Pylorospasm.  A 
number  of  observations  were  made  on  this  infant.    When  the  child 


HUNGER  IN  APPETITE  AND  DISEASE 


28s 


Fig.  36. — A,  tracing  showing  a  period  of  vigorous  hunger  contractions  of  the 
empty  stomach  of  a  normal  infant;  B,  tracing  showing  exceptionally  intense  and 
practically  continuous  hunger  contractions  of  a  3-months-old  infant  with  persistent 
pylorus  spasm  amounting  to  almost  complete  pyloric  obstruction  accompanied  by 
chronic  vomiting  and  gradual  loss  of  weight;  C,  tracing  showing  exceptionally  intense 
hunger  contractions  and  periods  of  incomplete  tetanus  of  the  empty  stomach  of  a 
5-months-old  infant  with  chronic  vomiting  ("rumination")  and  practically  stationary 
body  weight.  In  the  right  half  of  the  tracing  the  upward  excursion  of  the  manometer 
had  to  be  checked  mechanically  to  prevent  the  chloroform  from  being  driven  out. 
Hence  the  extreme  vigor  of  the  gastric  contractions  is  not  fully  registered.  Chloro- 
form manometer.    Time  20  minutes. 


286        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

was  quiet,  so  that  all  nervous  inhibitory  factors  were  eliminated, 
the  empty  stomach  usually  showed  hypertonus  with  periods  of 
tetanic  contractions  lasting  several  minutes,  interspersed  with 
vigorous  contractions  of  normal  duration — an  unmistakable  con- 
dition of  hypertonicity  and  hypermotility.  If  the  infant  was 
asleep  during  the  observation  period  the  tetanic  contraction  of 
the  stomach  invariably  caused  restless  facial  grimaces,  or  he  would 
wake  up  and  cry.  Such  vigorous  and  prolonged  periods  of  tetanic 
contractions  have  so  far  never  been  observed  in  the  empty  stomach 
of  normal  infants.  They  have  been  observed  in  adult  persons  and 
in  dogs  after  prolonged  starvation.  This  type  of  contractions  of 
the  empty  stomach  may  also  be  seen  in  dogs  with  pancreatic 
diabetes. 

The  results  in  the  cases  of  these  two  infants  indicate  that 
pylorospasm  and  pyloric  stenosis  involve  either  primarily  or 
secondarily  a  condition  of  hypertonus  and  hypermotility  of  the 
entire  stomach.  The  excessive  contraction  of  the  pylorus  may  be 
an  expression  of  this  general  hypermotility.  It  is  known  that  the 
tonus  and  contractions  of  stomachs  in  young  mammals  are  greater 
than  in  the  adult  and  in  the  old.  This  may  be  correlated  with  the 
greater  tendency  to  hyperactivity  of  the  pylorus  in  infancy  and 
childhood.  In  the  adult  these  gastric  contractions  would  cause 
intense  hunger  pains,  and  it  is  probable  that  such  pains  are  also 
experienced  by  the  infant. 

8.  Hunger  in  experimental  fevers  in  man  and  dogs.—T>r.  Rupp 
induced  temporary  fever  in  himself  and  in  a  number  of  other 
men  by  injections  of  typhoid  vaccines  and  of  sodium  nucleate. 
Records  of  the  gastric  hunger  contractions  were  taken  in  the 
usual  way,  and  careful  notes  made  of  the  subject's  own  feeling  of 
hunger  and  appetite.  Fever  reactions  on  injection  of  the  standard 
doses  of  typhoid  vaccine  are  usually  very  slight  and  variable,  but 
with  doses  two  or  three  times  larger  elevation  of  the  temperature 
up  to  103°  or  104°  F.  together  with  the  other  symptoms  of  fever 
can  usually  be  produced  for  a  few  hours.  Sodium  nucleate  in- 
variably brings  on  a  temporary  fever,  the  degree  and  duration  of 
the  fever  depending  on  the  quantity  injected. 


HUNGER  AND  APPETITE  IN  DISEASE 


287 


J   -4-1  en  tn 

^  :3  cs;:-, 


CQ 


288        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

Dr.  Rupp  found  that  when  the  temperature  elevation  reached 
only  ioo°-io2°  F.  the  strength  and  duration  of  the  gastric  hunger 
contractions  showed  practically  no  deviation  from  the  normal. 
But  they  produced  a  different  effect  on  consciousness.  Instead  of 
the  normal  hunger  pangs  associated  with  increased  appetite  and 
desire  for  food,  the  gastric  hunger  periods  during  the  fever  pro- 
duced headache,  nausea,  and  an  epigastric  distress  like  ''sick 
stomach."  More  severe  temperature  reactions  (104°-! 05°  F.) 
usually  render  the  empty  stomach  atonic,  and  in  that  condition 
there  are  no  hunger  contractions.  When  the  subjects  experienced 
the  fever  chills  there  was  always  complete  absence  of  the  gastric 
hunger   contractions. 

Similar  results  were  obtained  by  Dr.  Mayer  on  dogs.  Sodium 
nucleate  fevers  of  i03°-io5°  F.  lead  to  gastric  atony  and  absence 
of  the  hunger  contractions.  But  temperature  elevations  of  one 
or  two  degrees  above  the  normal  had  little  or  no  effect. 

It  must  be  noted  that  we  are  here  dealing  with  very  temporary 
fever  reactions.  It  is  not  unlikely  that  temperature  elevations  of 
one  or  two  degrees  above  the  normal  and  persisting  for  days  or 
weeks  would  have  a  more  deleterious  influence  on  the  gastric 
hunger  mechanism. 

These  experiments  show  that  fever  anorexia  is  in  some  cases  at 
least  more  complicated  than  the  mere  absence  of  the  gastric  hunger 
contractions.  In  fact  we  may  have  objectively  normal  gastric 
contractions  parallel  with  the  epigastric  feeling  of  "sick  stomach," 
nausea,  headache,  depression,  no  thought  of  or  desire  for  food. 
This  anomalous  condition  may  be  due  to  hyperexcitabihty  of  the 
gastric  sensory  nerves  by  action  of  the  toxins,  or  due  to  elevation 
of  the  temperature.  Changes  in  the  central  nervous  system  may 
also  play  a  role. 


CHAPTER  XVII 

HUNGER  AND  APPETITE  IN  DISEASE— {Coniinued) 

I.      ACTION  OF   BITTER  TONICS 

ACTION   ON  THE  HUNGER  MECHANISM 

The  value  of  "bitter  herbs"  in  disease  is  a  current  popular 
belief,  and  the  use  of  these  bitters  as  medicine  probably  antedates 
even  the  "medicine  man"  of  primitive  human  society.  Today 
the  use  of  bitters  is,  or  at  least  should  be,  confined  to  cases  of 
impaired  gastric  digestion.  The  mechanism  of  this  action  is  still 
in  the  main  an  open  question,  despite  a  considerable  amount  of 
\experimental  work.  The  literature  seems  to  show  that  the  bitters 
cause  increased  secretion  of  gastric  juice.  Nevertheless,  Cushny 
Concludes  that  the  favorable  effects  from  bitters  are  largely  sub- 
jective. The  bitters  are  capable  of  producing  a  considerable 
irtpression  on  the  patient,  so  that  their  effects  may  be  due  in  part 
to  suggestion  and  not  to  any  real  action  of  the  drug.  That  the 
bitters  increase  appetite  and  hunger  is  a  generally  accepted  view. 
Th^  bitters  may  produce  these  results  in  any  or  all  of  the  following 
way^:  (i)  direct  inauguration  or  augmentation  of  the  hunger 
contractions  of  the  empty  stomach,  or  hastening  the  reappearance 
of  the  gastric  hunger  contractions  by  facihtating  gastric  digestion 
(through  increased  secretion  or  increased  peristalsis),  and  thus 
accelerating  the  emptying  of  the  stomach;  (2)  augmentation  of 
appetiip  directly  by  stimulation  of  gustatory  and  other  sensory 
nerves  in  the  mouth,  esophagus,  and  stomach,  or  indirectly,  by 
accelerating  gastric  digestion;  (3)  central  Bahnung  or  facilitation, 
the  stroiig  afferent  impulses  from  the  mouth  (and  possibly  also 
from  the\  esophagus  and  stomach)  may  in  some  way  bring  feeble 
hunger  an^  appetite  sensations  more  prominently  into  consciousness. 

The  teUs  were  carried  out  on  a  number  of  normal  men,  and  the 
influence  of  the  bitters  in  the  mouth  and  in  the  stomach  was  tested 
separately.  \  The  bitters  were  introduced  through  the  stomach  tube 

289 


290        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

when  it  was  desired  to  study  the  action  from  the  stomach  alone. 
In  Mr.  v.,  and  usually  also  in  the  dogs,  the  drugs  were  introduced 
through  the  gastric  fistula. 

In  order  to  exclude  possible  psychic  factors,  the  subject  was 
frequently  kept  in  ignorance  of  the  nature  of  the  substance  (water 
or  drug)  as  well  as  of  the  time  when  it  was  given. 

The  following  bitters  were  used:  tinctures  of  gentian,  quassia, 
columba,  humulus,  and  condurango;  ehxir  of  quinine,  strychnine, 
and  iron. 

In  the  case  of  man  the  bitters  were  introduced  into  the  stomach 
in  varying  quantities  up  to  the  maximum  therapeutic  dose,  but 
never  exceeding  that.  In  the  case  of  the  dogs  the  drugs  were  used  in 
gradually  increasing  quantities  until  definite  effects  were  produced. 

I.  Action  in  the  stomach. — When  used  in  therapeutic  quantities 
and  introduced  directly  into  the  stomach  so  as  not  to  come  into 
contact  with  the  mouth  or  esophagus,  these  bitters  have  no  direct 
action  whatever  on  the  hunger  mechanism.  If  the  bitters  are 
introduced  into  the  stomach  during  a  hunger  period,  the  gastric 
hunger  contractions  continue  in  their  normal  rate  and  strength 
until  the  completion  of  the  hunger  period,  except  for  a  slight 
temporary  inhibition  that  may  appear  immediately  on  introduction 
of  the  drug.  This  transient  inhibition  is  not  peculiar  to  these  drugs, 
however,  since  it  follows  the  introduction  of  any  liquid,  including 
water  at  body  temperature,  directly  into  the  stomach.  At  no 
time  did  we  obtain  an  increase  in  the  gastric  hunger  contractions 
from  the  bitters.  If  the  bitters  are  introduced  into  the  empty  but 
quiescent  stomach,  that  is,  between  two  hunger  periods,  there  is 
no  immediate  initiation  of  gastric  hunger  contractions  or  hastening 
of  the  appearance  of  the  next  hunger  period. 

The  foregoing  results  were  obtained  with  all  the  bitters  both 
in  man  and  dogs,  so  that  we  are  inclined  to  believe  that  all  the 
numerous  bitters  used  in  therapeutics  are  without  direct  action 
(that  is  from  the.  stomach)  on  the  hunger  mechanism  when  used  in 
therapeutic  quantities. 

When  the  bitters  are  introduced  directly  into  the  stomach  in 
sufficient  quantities  to  produce  demonstrable  effects  on  the  hunger 


HUNGER  AND  APPETITE  IN  DISEASE 


291 


mechanism,  this  action  is  always 
in  the  direction  of  inhibition, 
and  the  inhibition  is  the  greater 
the  greater  the  quantity  of  the 
drug.  All  the  bitters  tried  are 
capable  of  causing  this  inhibition 
of  hunger.  It  is  not  known  what 
ingredient  in  the  bitters  is 
responsible  for  this  action.  The 
alcohol  in  the  tinctures  will  itself 
produce  some  inhibition.  This 
inhibition  is  not  peculiar  to  the 
bitters,  as  previous  work  has 
shown  that  anything  which 
stimulates  the  nerve-endings  in 
the  gastric  mucosa  inhibits  the 
gastric  hunger  mechanism  in 
proportion  to  the  intensity  and 
duration  of  the  stimulation. 
And  it  is  of  little  or  no  interest 
in  therapeutics,  as  the  quanti- 
ties of  the  drugs  required  to 
produce  it  are  much  greater 
than  that  permissible  in^  practi- 
cal medicine.  When  the  elixir 
of  iron,  quinine,  and  strychnine 
is  put  into  the  stomach  in 
quantities  sufficient  to  affect 
the  hunger  mechanism,  the  ani- 
mal usually  develops  mild  symp- 
toms of  strychnine  poisoning 
(rapid  respiration,  greatly  in- 
creased reflex  excitability). 
During  this  period  of  increased 
activity  of  the  skeletal  neuro- 
muscular mechanisms,  there  is 


292        CONTROL  OF  HtJNGER  IN  HEALTH  AND  DISEASE 

not  only  no  increase  in  tonus  and  hunger  contractions  of  the 
empty  stomach,  but  the  stomach  is  rendered  even  more  atonic 
than  during  the  quiescent  interval  between  the  hunger  periods  in 
the  normal  animal,  a  situation  similar  to  that  found  in  animals  in 
parathyroid  tetany.  According  to  Heubner  and  Reider,  large 
doses  of  bitters  retard  the  emptying  of  the  stomach  in  digestion. 

2.  Action  in  the  mouth. ^The  experiments  on  dogs  were  unsatis- 
factory and  inconclusive,  for  the  reason  that  the  dogs  object  to  the 
bitters,  even  when  given  in  minute  quantities  by  the  mouth.  The 
dogs  salivate  profusely,  become  restless,  and  endeavor  in  various 
ways  to  get  rid  of  the  apparently  disagreeable  taste  of  the  bitters. 
Putting  small  quantities  of  the  bitters  in  the  mouth  invariably 
leads  to  prompt  and  prolonged  inhibition  of  the  gastric  hunger 
contractions,  but  inhibition  of  the  hunger  pangs  in  dogs  accompanies 
restlessness  of  the  animal  from  any  cause.  The  results  on  man 
are  not  comphcated  by  the  uncontrollable  factor  of  strugghng  and 
protest. 

In  man  the  bitters  acting  in  the  mouth  inhibit  the  gastric  hunger 
contractions  in  direct  proportion  to  the  intensity  of  their  stimu- 
lation of  taste  sense.  If  the  bitters  are  placed  in  the  mouth  during 
a  period  of  quiescence  of  the  empty  stomach,  there  is  no  initiation 
of  gastric  hunger  contractions,  but  so  far  as  any  effect  can  be 
detected  this  is  a  temporary  inhibition  of  the  gastric  tonus.  The 
temporary  inhibition  of  the  gastric  tonus  and  hunger  contractions 
by  the  bitters  acting  in  the  mouth  is  not  followed  by  an  increase 
in  gastric  tonus  or  gastric  hunger  contractions  above  the  normal. 
That  is,  there  is  no  after-effect  of  the  nature  of  augmentation  or 
stimulation  of  the  hunger  mechanism.  A  few  drops  of  tincture  of 
condurango  on  the  tongue  may  inhibit  the  hunger  contractions 
for  15  to  20  minutes. 

We  think  that  a  sufficient  number  of  bitters  is  included  in  the 
experiments  above  to  justify  applying  the  results  to  the  whole 
group  of  bitters,  especially  in  view  of  the  fact  that  the  action  on 
the  hunger  mechanism  is  the  same  in  all  cases. 

These  experiments  were  conducted  on  normal  individuals, 
while  the  bitters  are  or  should  be  prescribed  only  in  cases  of  anorexia, 


HUNGER  AND  APPETITE  IN  DISEASE  293 

a  disordered  digestion,  or  particularly  a  disordered  gastric  digestion. 
There  remains  the  possibiHty  of  a  more  favorable  action  of  the 
bitters  on  the  hunger  mechanism  in  these  pathological  conditions. 
It  is  desirable  that  direct  tests  be  made  on  such  material  with 
proper  control.  But  we  venture  to  predict  that  the  results  will  be 
the  same  as  those  reported  above  on  normal  men,  as  it  is  not  likely 
that  the  fundamental  reflex  relations  of  the  sensory  nerves  in  the 
mouth  and  the  gastric  mucosa  to  the  hunger  mechanism  are  so 
readily  changed  by  disease. 

It  must  be  noted  that  the  reflex  inhibition  of  the  hunger  con- 
tractions from  the  actions  of  the  bitters  in  the  mouth  is  accompanied 
by  cessation  of  the  conscious  hunger  pangs.  There  is  a  complete 
parallel  between  the  objective  inhibition  and  the  subjective  absence 
of  hunger  sensation. 

The  foregoing  results  show  clearly  that  the  bitters  usually  em- 
ployed in  therapeutics  have  no  favorable  action  on  the  hunger 
mechanism.  But  the  therapeutic  use  of  these  substances  may  still 
be  justified  by  their  direct  action  on  gastric  secretion  or  on  the 
appetite. 

Summarizing,  we  conclude  that  in  therapeutic  quantities  the 
bitters,  acting  in  the  stomach  alone,  have  no  effect  on  the  gastric 
tonus  or  the  gastric  hunger  contractions  or  on  the  parallel  sensation 
of  hunger.  In  greater  than  therapeutic  doses  the  bitters  inhibit 
the  hunger  contractions  and  abolish  the  hunger  sensations,  prob- 
ably by  stimulation  of  nerve-endings  in  the  gastric  mucosa.  Acting 
in  the  mouth  alone,  the  bitters,  even  in  traces,  inhibit  the  hunger 
contractions  and  abolish  the  hunger  sensations  in  direct  proportion 
to  the  intensity  and  duration  of  the  stimulation  in  the  mouth,  and 
there  is  no  after-effect  in  the  way  of  augmentation  of  hunger 
contractions  and  hunger  sensations. 

II.      ACTION  ON  THE   SECRETION   OF   GASTRIC  JUICE  IN 
NORMAL  MEN  AND  DOGS 

The  literature  on  this  subject  is  both  considerable  and  conflict- 
ing. It  seems  pretty  well  estabhshed  that  the  bitters  have  no  action 
on  the  pepsin-hydrochloric-acid  digestion  itself,  except  possibly  in 


294        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

way  of  slight  retardation.  This  sKght  retarding  action  is  of  no 
practical  significance,  especially  when  the  bitters  are  taken  20  or 
30  minutes  before  the  meal,  or  even  just  before  the  meal,  because 
of  the  great  dilution  with  gastric  juice,  saliva,  and  the  fluids  of  the 
food.  The  literature  also  points  to  the  conclusion  that  by  them- 
selves the  bitter  tonics  are  incapable  of  causing  secretion  of  gastric 
juice,  either  by  acting  in  the  mouth  or  in  the  stomach.  Pavlov 
noted  in  dogs  that  the  bitters  acting  in  the  mouth  cause  a  copious 
flow  of  saliva,  but  leave  the  gastric  gland  perfectly  quiescent;  and 
not  even  when  introduced  into  the  stomach  do  they  cause  secretion 
of  gastric  juice. 

Some  observers  (Reichmann,  Scheffer,  and  others)  have  reported 
that  as  long  as  the  bitters  remain  in  the  stomach  they  depress  or 
diminish  the  secretion  of  gastric  juice,  and  this  led  to  giving  the 
bitters  from  10  to  30  minutes  before  the  meals. 

Do  the  bitter  tonics  augment  the  secretion  of  gastric  juice 
indirectly  by  increasing  the  excitability  of  the  nerve-endings  of 
taste  in  the  mouth,  and  possibly  the  nerves  of  appetite  sense  in  the 
stomach  ?  This  is  the  view  emphasized  by  Pavlov,  but  he  does  not 
adduce  any  experiments  in  its  support.  The  work  of  Borissow 
seems  to  confirm  it,  however.  Borissow  reports  12  sham-feeding 
tests  on  one  dog  with  gastric  fistula  and  esophagotomy.  Six  of 
these  tests  were  made  after  giving  the  dog  tincture  of  gentian 
in  the  mouth.  In  both  series  of  tests  the  sham  feeding  was  con- 
tinued for  I  minute  and  the  gastric  juice  collected  for  2  hours 
following  the  sham  meal.  In  the  case  of  the  gentian  series,  the 
sham  feeding  was  instituted  as  soon  as  the  profuse  salivation 
induced  by  the  bitters  had  ceased.  Borissow  obtained  the  following 
results : 


Series 

Min.  c.c. 

Max.  c.c. 

Aver.  c.c. 

Normal  or  no  tonic 

Tincture  of  gentian 

59-3 
85-1 

126.5 
185.2 

lOI 

130 

There  was  no  dift'erence  in  the  acidity  and  the  pepsin  concen- 
tration of  the  gastric  juice  of  the  two  series,  but  the  average  excess 


HUNGER  AND  APPETITE  IN  DISEASE  295 

of  gastric  juice  in  the  gentian  series  is  striking.  However,  it  may 
be  questioned  whether  a  short  series  of  tests  on  one  animal  can  be 
held  as  conclusive,  especially  in  view  of  the  great  individual 
variations  (over  100  per  cent)  within  each  series. 

Experimental  procedure  on  man. — It  will  be  recalled  that  Mr.  V. 
has  the  esophagus  completely  restricted  at  the  level  of  the  upper 
end  of  the  sternum,  so  that  nothing  can  be  swallowed  from  the 
mouth  and  reach  the  stomach  via  the  esophagus.  Above  the 
constriction  the  esophagus  is  somewhat  dilated  so  as  to  hold 
about  half  a  glass  of  liquid.  These  conditions  serve  admirably 
for  studying  the  influence  of  the  bitters  on  the  secretion  of  gastric 
juice. 

On  all  test  days  100  c.c.  of  water  were  put  into  the  stomach 
120  and  60  minutes  before  the  meal,  so  as  to  insure  a  completely 
empty  stomach.  The  tonics  were  introduced  into  the  stomach  via 
the  fistula  15  to  30  minutes  before  mealtime.  In  the  series  of  tests 
with  the  tonics  in  the  mouth,  these  were  put  into  the  mouth  and 
swallowed  into  the  esophageal  pouch  10  minutes  before  the  meal. 
They  usually  had  to  be  expectorated  before  the  meal  actually 
began,  because  of  the  salivation  induced  by  them. 

In  all  three  series  of  tests  the  gastric  juice  was  collected  in  the 
course  of  the  first  20  minutes  during  which  Mr.  V.  was  chewing  his 
food  in  the  usual  way,  preparatory  to  putting  it  into  the  stomach 
by  means  of  a  syringe.  We  are  therefore  dealing  with  the  appetite 
gastric  secretion  only. 

The  stomach  was  invariably  emptied  just  before  Mr.  V.  started 
to  eat,  and  a  record  was  kept  of  the  quantity,  acidity,  and  pepsin 
strength  of  this  juice  found  in  the  empty  stomach,  as  it  was  thought 
that  the  quantity  and  quality  of  this  juice  might  serve  to  indicate 
the  physiologic  condition  of  the  gastric  glands,  irrespective  of  the 
condition  of  the  appetite. 

The  experiments  were  made  during  the  period  from  April  to 
November,  19 14.  The  tests  with  the  tonics  were  interspersed  with 
controls  without  the  tonics  all  the  way,  so  as  to  eliminate  as  far  as 
possible  the  errors  from  variations  in  nutrition,  appetite,  etc., 
associated  with  variations  in  climate  and  bodily  activity. 


296        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 


It  was  aimed  to  make  these  tests  a  mere  incident  in  Mr.  V.'s 
daily  routine.  For  that  reason  no  special  dietary  standard  was 
fixed.  The  ingredients  of  the  noonday  meal  Mr.  V.  selected  for 
himself  at  a  nearby  cafeteria.  He  naturally  selected  what  appeared 
to  him  most  palatable  from  day  to  day.  The  evening  meal  was 
taken  in  the  same  boarding-house  throughout  the  experimental 
period.  Mr.  V.  stated  that  the  boarding-house  meals  were  very 
much  the  same  from  week  to  week,  and  were  kss  palatable  than 
the  noonday  meal. 

The  tonics  used  (in  therapeutic  doses)  were  tinctures  of  gentian, 
quassia,  columba,  humulus,  and  condurango,  and  elixir  of  quinine, 
strychnine,  and  iron.  Most  of  the  tests  were  made  with  the  gen- 
tian tincture  and  with  the  elixir. 

In  order  to  exclude  all  possible  psychic  factors,  Mr.  V.  was  not 

told  of  the  purpose  of  the  experiments.    He  went  about  his  daily 

work,  taking  his  usual  food  at  the  usual  time,  while  now  and  then 

a  tonic  was  given  and  the  appetite  secretion  measured.    We  think 

it  may  safely  be  concluded  that  such  psychic  factors  as  faith  in 

the  potency  of  or  hope  of  improvement  from  the  drugs  was  entirely 

eliminated.     Nor  was  the  taking  of  any  of  these  tonics  by  the 

mouth  disagreeable  or  loathsome,  such  as  might  induce  psychic 

depression. 

TABLE  V 

Gastric  Juice  Secreted  by  Mr.  V.  during  the  First  Twenty 
Minutes  of  Chewing  Food 


Tonics 

No.  OF  Ex- 
periments 

Gastric  Juice  in  c.c. 

Meal 

Lowest 

Highest 

Average 

Lunch  1 2:00-1:00  P.M. 
Supper  6:00-7:00  P.M. 

fNo  tonics 

j  Tonics  in  mouth . . . 
(Tonics  in  stomach . 

1  No  tonics 

j  Tonics  in  mouth, .  . 
[Tonics  in  stomach . 

31 
30 
20 
20 
20 
15 

35 
30 
40 
20 
20 
18 

95 
93 
85 
50 
48 
47 

58.0 
61.0 
58:2 
36.0 
330 
30.1 

Tests  to  the  number  of  50  were  made  with  bitters  in  the  mouth, 
and  35  with  bitters  in  the  stomach,  together  with  51  control  tests. 
These  are  summarized  in  tables.    The  lunch  and  supper  series  are 


HUNGER  AND  APPETITE  IN  DISEASE  297 

tabulated  separately,  because  the  appetite  gastric  secretion  was 
uniformly  less  at  the  evening  meal.  This  is  probably  due  to  less 
palatable  food  at  the  evening  meal  (absence  of  variety  in  the  food, 
inferior  cooking) . 

Examination  of  the  tables  shows  that  the  bitter  tonics  acting 
either  in  the  stomach  or  in  the  mouth  are  without  influence  on  the 
quantity  of  the  appetite  psychic  secretion.  There  is  a  suggestion 
of  an  increased  secretion  with  the  bitters  in  the  mouth  for  the 
noonday  series,  but  this  is  counterbalanced  by  a  shghtly  lower 
figure  for  the  evening  meal.  The  average  physiologic  condition 
of  the  gastric  glands  is  practically  the  same  in  all  the  series. 

As  Mr.  V.  is  a  young  man  in  good  health,  the  question  naturally 
arises  whether  the  sensory  nerves  for  the  appetite  sense  (in  mouth 
and  stomach)  are  not  normally  in  a  state  of  maximum  excitability, 
so  that  no  further  increase  in  excitability  by  bitter  tonics  is  possible. 
This  objection  seems  to  be  met  by  the  lower  secretion  at  the  evening 
meal.  Here  is  a  condition  in  which  less  palatable  food  should  have 
been  rendered  more  palatable  by  contrast  with  the  bitter  tonic,  or 
by  actual  increase  in  the  excitability  of  the  gustatory  nerves.  The 
results  indicate  no  improvement  by  contrast.  If  the  bitters  in  the 
mouth  augmented  the  excitability  of  the  taste  nerves  at  the  evening 
meal,  this  evidently  caused  an  already  unpalatable  food  to  taste 
still  more  unpalatable,  and  hence  the  diminished  appetite  secretion. 

These  bitters  in  mouth  or  stomach  produced  no  change  in  the 
acidity  and  in  the  pepsin  concentration  of  the  appetite  gastric  juice. 

A  similar  series  of  tests  was  made  on  eight  dogs  provided  with 
an  accessory  stomach  pouch,  according  to  the  Heidenhain-Pavlov 
method.  Care  was  taken  to  interfere  as  little  as  possible  with  the 
distribution  of  the  vagi  to  the  stomach  pouch. 

The  tonics  were  introduced  into  the  main  stomach  by  iheans 
of  a  stomach  tube,  so  as  not  to  come  in  contact  with  the  nerve- 
endings  in  the  mouth  or  esophagus.  They  were  introduced  into  the 
stomach  pouch  directly  with  a  pipette.  When  introduced  into  the 
mouth  the  bitters  were  soaked  up  in  a  small  wad  of  cotton  and 
the  dog  was  compelled  to  chew  on  this  for  i  minute.  The  tests  were 
made  24  hours  after  the  previous  meal,  and  each  dog  was  fed  a 


298        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

fixed  quantity  of  boiled  lean  meat.  The  gastric  juice  was  collected 
for  2  hours  after  the  beginning  of  the  feeding. 

The  tonics  were  put  into  the  main  and  accessory  stomachs  from 
20  to  30  minutes  before  feeding,  and  into  the  mouth  10  minutes 
before  feeding.  The  size  of  the  dogs  varied  from  5  to  8  kg.  The 
quantity  of  tonics  put  into  the  stomach  varied  from  1.5  to  2  c.c. 

Our  results  on  the  five  dogs  are  summarized  in  Table  VI.  The 
data  in  this  table  permit  only  one  conclusion,  namely,  that  these 
bitters  acting  in  the  mouth  or  in  the  stomach  have  no  effect  on 
the  secretion  of  gastric  juice  or  on  the  quantity  of  food  consumed 
by  the  normal  dog.  The  sHght  increase  that  appears  in  the  case  of 
Dog  5  would  probably  have  been  counterbalanced  if  a  larger  series 
of  tests  had  been  made.  The  tonics  did  not  produce  any  changes 
in  the  acidity  and  pepsin  concentration. 

TABLE  VI* 


Dog 

Tonics 

No.  OF  Ex- 
periments 

Gastric  Juice  in  c.c. 

Lowest 

Highest 

Average 

[No  tonics 

17 
IS 
IS 

17 

'   10 

10 

IS 
10 
10 

6 
6 

10 

9 
8 

10 

13 
10 

3 
3 
2 

4 
5 
3 

6 
S 

8 

7 
7 

33 
29 
26 

9 
8 

7 

10 
10 

8 

9 
II 

16 

17 
16 

19.0 
18.4 
18  6 

Dog  I .  . 

I  Tonics  in  mouth 

[Tonics  in  main  stomach 

fNo  tonics 

s'l 

4-9 
4.8 

7.0 
7.2 
6.8 

8.4 
8.0 

12  2 

Dog  2 .  . 

\  Tonics  in  mouth 

Tonics  in  main  stomach 

fNo  tonics 

Dog  3.. 
Dog  4.. 

■  Tonics  in  mouth. 

Tonics  in  main  stomach 

/No  tonics 

\Tonics  in  main  stomach 

fNo  tonics          .        

Dogs.. 

Tonics  in  main  stomach 

Tonics  in  small  stomach 

14.0 
14. 1 

*Dogs  with  accessory  stomachs  prepared  according  to  the  Heidenhain-Pavlov  method.  Record 
of  the  secretion  of  gastric  juice  for  the  first  two  hours  following  a  standard  meal  of  lean  meat.  The  va- 
riation in  the  average  quantity  of  gastric  juice  secreted  by  the  different  dogs  is  due  mainly  to  difference 
in  size  of  the  accessory  stomachs. 


The  possible  value  of  these  and  other  stomachics,  especially  in 
digestive  disorders,  should  be  investigated  by  other  methods,  such 
as  the  determination  of  the  actual  quantity  of  food  consumed,  the 


HUNGER  AND  APPETITE  IN  DISEASE 


299 


time  required  for  completion  of  gastric  digestion,  etc.,  with  and 
without  the  tonics.  And  the  final  verdict  cannot  be  given  until 
all  possible  tests  have  been  applied.  But  as  regards  any  favorable 
action  of  these  stomachics  on  the  gastric  secretory  mechanism  in 
normal  men  and  dogs  our  results  go  to  show  that  it  is  nil,  at  least 
when  all  purely  psychic  factors  are  eliminated. 


III.      INFLUENCE   ON  FOOD   CONSUMPTION  AND   ON   THE 
GASTRIC  JUICE   IN  EXPERIMENTAL  CACHEXIA 

Hoppe  reports  that  when  bitters  are  given  to  sick  dogs  the 
quantity  of  gastric  juice  is  increased,  and  the  pepsin  and  HCl  of 
the  juice  is  likewise  increased.  No  figures  are  presented,  nor  are 
sufficient  accounts  of  the  method  used  given,  so  as  to  enable  one 
to  evaluate  his  conclusions.  Moorhead,  working  in  the  author's 
laboratory,  produced  cachexia  in  two  dogs  with  Pavlov  stomach 
pouch  by  repeated  excessive  hemorrhage,  and  studied  the  action 
of  the  bitters  on  the  food  consumption  and  the  appetite  secretion 
before  and  after  inducing  the  chronic  anemia.  The  dogs  were  bled 
20  to  30  c.c.  per  kg.  daily  until  they  became  permanently  listless, 
weak,  and  depressed,  lost  weight  gradually,  and  showed  little 
interest  in  food  or  surroundings — ^in  a  word,  typically  cachectic. 
During  the  observation  period  the  dogs  showed  little  or  no 
improvement. 

TABLE  VII 
Quantity  of  Gastric  Secretion  in  c.c,  Cachectic  Dogs  (Pavlov  Stomach) 


No.  T. 

Dog  I 

Dog  2 

Series 

Avr. 

Mxm. 

Mnm. 

Avr. 

Mxm. 

Mnm. 

Appetite     secre-i 
tion  one  hour. . 

First  hour  after 
feeding 

No  tonics 

Tonics  in  mouth  . .  . 
Tonics  in  stomach  . 

No  tonics 

Tonics  in  mouth  . . . 
Tonics  in  stomach  . 

10 
10 
10 

10 
10 
10 

0.50 
1.90 
1.06 

2.50 
I.  20 

2.0 
4.2 
31 

3-9 
50 

35 

0.0 

0.0 

0.0 
0.2 
0.2 

115 
1. 14 
1. 14 

ISO 
315 
1.80 

S-o 

2.1 
2.2 

S-9 

7-7 

2-5 

0.0 
O.I 
0.0 

0.0 
O.I 

0.1 

Before  the  chronic  anemia  was  induced  the  bitters  had  no 
influence  on  food  consumption  or  on  the  quality  and  quantity  of 


300        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

the  appetite  gastric  juice.  During  the  cachexia  the  bitters  acting 
in  the  mouth  appeared  to  increase  sKghtly  both  the  quantity  of 
food  consumed,  and  the  quantity  and  quahty  of  the  appetite 
gastric  juice  (Table  VII).  The  experiments  are  not  numerous 
enough  to  permit  final  conclusions,  even  for  sick  dogs.  And  it  is 
not  clear  whether  the  apparent  action  of  the  bitters  is  a  direct  one 
on  the  appetite  mechanism,  or  in  the  nature  of  a  condition  reflex. 
The  real  value  of  bitter  tonics  as  stimuli  to  appetite  in  disease  is 
still  an  open  question,  that  must  be  answered  by  quantitative  test 
methods  on  the  sick. 

IV.      ACTION   ON  APPETITE   IN  CLINICAL  CACHEXIA 

Moorhead  has  completed  an  extensive  series  of  tests  with  bitters 
on  five  hospital  patients  with  chronic  cachexia  and  poor  appetite, 
using  the  method  of  weighing  the  food  consumed,  on  the  theory 
that  if  the  bitters  actually  increase  appetite  this  should  be  revealed 
in  the  food  consumption.  Tonic  days  were  alternated  with  no-tonic 
days,  so  as  to  exclude  any  progressive  increase  or  decrease  in  the 
appetite  from  other  causes.    The  results  are  as  follows: 

Patient  A:  given  tincture  of  gentian.  The  patient  was  told 
that  the  medicine  would  help  his  appetite  and  digestion,  and 
said  he  felt  that  it  did  improve  his  appetite  a  great  deal.  Evidently 
the  subjective  faith  and  hope  was  greater  than  the  objective  results. 

Number  of  control  or  no- tonic  meals 45 

Number  of  tonic  meals 87 

Average  food  consumption,  no-tonic  meals ....  10. 3  oz. 
Average  food  consumption,  tonic  meals 1 1 . 3  oz. 

Average  increase i  oz.  per  meal 

Patient  B :  given  elixir  of  iron,  quinine,  and  strychnine.  This 
patient  was  not  told  what  the  medicine  was  given  for,  hence  he 
did  not  know  that  any  attempts  were  made  to  improve  his  appetite. 

Number  of  control  or  no-tonic  meals 60 

Nutnber  of  tonic  meals 48  . 

Average  food  consumption,  no-tonic  meals .  .  . .  1 1 . 8  oz. 
Average  food  consumption,  or  tonic  meals 13 . 8  oz. 

Average  increase 2  oz.  per  meal 


HUNGER  AND  APPETITE  IN  DISEASE  301 

Patient  C :  given  elixir  of  iron,  quinine,  and  strychnine,  without 
being  told  for  what  purpose.  This  patient  was  a  chronic  alcohoHc 
and  cachectic,  with  no  other  definite  ailment. 

Number  of  control  or  no-tonic  meals 33 

Number  of  tonic  meals 27 

Average  food  consumption,  no-tonic  meals.  .  .  .9.95  oz. 
Average  food  consumption,  tonic  meals 10. 84  oz. 

Average  increase o.  89  oz.  per  meal 

Patient  D:  given  elixir  of  iron,  quinine,  and  strychnine.  This 
patient  had  chronic  myocarditis,  and  was  anemic  and  cachectic. 

Number  of  control  or  no  tonic  meals 32 

Number  of  tonic  meals 37 

Average  food  consumption,  no  tonic  meals 1 1 . 7  oz. 

Average  food  consumption,  tonic  meals 13 .  2  oz. 

Average  increase  i .  5  oz. 

Patient  E:  given  tincture  of  gentian.  This  patient  had  per- 
nicious anemia,  and  was  very  emaciated.  He  was  told  that  the 
medicine  given  him  would  improve  his  appetite,  and  he  was  very 
anxious  to  have  his  appetite  improved. 

Number  of  control  or  no  tonic  meals 22 

Number  of  tonic  meals 21 

Average  food  consumption,  no  tonic  meals. ...  19.4  oz. 
Average  food  consumption,  tonic  meals 23 .  i  oz. 

Average  increase 3  •  7  oz. 

The  number  of  different  kinds  of  bitters  advocated  from  time 
to  time  as  useful  in  disease  is  a  large  one.  They  are  of  such  varied 
chemical  composition  that  the  only  thing  they  have  in  common  is 
the  bitter  taste.  Of  course,  in  this  discussion,  we  do  not  include 
such  substances  as  quinine  or  strychnine,  or  the  bitters  with  alcohol 
as  the  main  constituent,  as  these  substances  have  distinct  physio- 
logic actions  not  directly  related  to  appetite,  after  absorption  into 
the  blood. 

The  bitter  tonics  are  common  ''home  remedies"  and  favorite 
"drug-counter  prescriptions."  They  are  given  to  convalescents 
who  would  continue  to  improve,  tonic  or  no  tonic,  and  the  tonic, 


302        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 

not  the  recuperative  power  of  the  patient,  gets  the  credit,  or  the 
physician  prescribes  a  more  hygienic  Hving  and  a  tonic.  The  health 
improves  and  both  physician  and  patient  think  the  tonic  did  it. 

But  even  if  the  bitters  have  no  direct  action  on  gastric  secretion 
and  digestion,  and  no  appreciable  indirect  action  on  the  secretion  of 
gastric  juice,  may  they  not  be  valuable  aids  in  expelling  worry  and 
implanting  hope  and  good  cheer  in  the  mind  of  the  patient  ?  May 
they  not  be  an  efficient  handmaid  to  psychotherapy?  There  is 
no  question  that  the  bitter  tonics  connect  up  with  the  popular 
belief  that  the  potency  of  a  medicine  is  directly  related  to  its 
strong  (or  bad)  taste.  And  the  readiness  with  which  these  tonics 
are  dispensed  nourishes  the  popular  superstition  that  there  is,  or 
must  be,  a  specific  drug  remedy  for  every  ailment,  a  superstition 
that  constitutes  the  chief  aid  of  the  medical  quack  and  the  patent 
medicine  vender. 

The  stimulation  of  certain  nerve-endings  in  the  mouth  and  in 
the  normal  gastric  mucosa  unquestionably  contributes  to  the  com- 
plex sensation  of  appetite,  and  these  nerves  are  stimulated  by 
condiments  and  flavors  of  food.  Apart  from  this,  the  physiologic 
way  of  augmenting  hunger  and  appetite  is  moderation  in  the  food 
intake  or  increasing  the  utilization  of  the  food  in  the  body  by  outdoor 
living,  fresh  air,  cold  baths,  and  physical  work.  If  these  measures 
do  not  improve  appetite  and  hunger,  the  chances  are  that  the 
digestive  tract  is  not  in  a  condition  to  take  care  of  the  amount  of 
food  demanded  by  stronger  hunger  and  appetite  sensations. 


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INDEX 


Abdomen,  effect  of  massage  of,  on  hun- 
ger, 200. 

Acidity  of  human  gastric  juice,  254. 

Acids,  in  stomach,  influence  of,  on  hun- 
ger, 171,  175. 

Age,  variations  in  hunger  with,  119. 

iVkoria,  266. 

Alcohol:  influence  of,  on  appetite,  180; 
on  hunger,  178. 

Alcoholic  gastritis,  hunger  and  appetite 
in,  271. 

x\lkalies  in  stomach,  influence  of,  on  hun- 
ger, 171,  265. 

Allotriophagia,  267. 

Ammino  acids,  in  gastric  juice,  253. 

Ammonia,  in  gastric  juice,  251. 

Animal  behavior,  influence  on,  of  hunger, 
8,  134,  136,  144,  147- 

Anorexia,  266,  286, 

Appetite:  gastric  factors  in,  99,  115;  in- 
heritance, factors  in,  11;  in  disease, 
261;  in  fevers,  278,  286;  in  prolonged 
starvation,  134;  nature  of,  98;  per- 
verted, 267;  relation  of,  to  hunger,  10, 
98;  relation  of,  to  thirst,  12;  theories 
of,  96. 

Appetite  gastric  juice:  acidity  of,  254; 
chemistry  of,  248;  importance  of,  in 
normal  digestion,  247;  secretion  of, 
235,  240. 

Bile,  in  stomach,  132. 

Bitter  tonics:  influence  of,  on  hunger, 
290;  on  food  consumption,  300;  on 
gastric  juice  secretion,  293;  nature  of 
action  of,  289,  302. 

Boldyreff,  work  of,  on  stomach  in  hunger, 
27,  33- 

Borborygmi,  in  hunger,  26,  82. 

Boring,  work  of,  on  hunger,  25,  105. 

Brain,  hunger  centers  in,  20, 149,  215,  216. 

Bulimia:  in  duodenal  fistula,  24;  in  re- 
section of  stomach,  23;  in  various 
diseases,  2O1. 

Busch,  work  of,  on  hunger,  24. 


Cachexia,  action  of  bitter  tonics  in,  299, 
300. 

Cannon,  work  of,  on  hunger,  19,  28,  35, 

Carbon  dioxide  in  stomach,  influence  of, 
on  hunger,  180. 

Cardia,  in  hunger,  77. 

Chemotropism,  in  appetite,  11,  99. 

Cerebrum:  influence  of,  on  hunger  con- 
tractions, 149;  hunger  centers  in,  216. 

Cold,  effect  of,  on  hunger,  7,  9,  206,  211. 

Continuous  secretion  of  gastric  juice,  233, 
234- 

Crop,  hunger  contractions  of,  in  birds,  51. 

Diabetes  mellitus,  hunger  in,  279. 

Diabetic  blood,  influence  of,  on  hunger, 

220. 

Disease,  hunger  and  appetite  in,  261. 

Distemper,  hunger  in,  273. 

Drugs,  influence  of,  on  hunger,  229. 

Emotions,  influence  of,  on  hunger,  151, 
182. 

Epigastric  "emptiness,"  feeling  of,  in 
hunger,  93. 

Epinephrin,  influence  of,  on  hunger,  229. 
Esophagus:    in  hunger,  7,  71,  81;   sensi- 
bility of,  104. 

Fevers,  hunger  and  appetite  in,  278,  286. 

Gall-bladder  infections,  gastric  pain  in, 
283. 

Gastric  cancer,  hunger  in,  280. 

Gastric  hunger  contractions:  after  sec- 
tion of  stomach  nerves,  141 ;  chemical 
control  of,  217;  effect  of  hemorrhage 
on,  222;  in  dogs,  138;  in  infants,  40, 
119;  in  man,  36,  126;  in  rabbits,  143; 
inreptilia,53; 

— conditions  of  disease:  alcoholic  gastri- 
tis, 271;  diabetes  mellitus,  277;  dis- 
temper, 273;  fevers,  276,  286;  gall- 
bladder infections,  283;  gastric  cancer, 
280;  gastric  ulcer,  281;  gastritis,  278; 


317 


3i8        CONTROL  OF  HUNGER  IN  HEALTH  AND  DISEASE 


mange,  268;  pancreatic  diabetes,  268; 
paro thyroid  tetany,  273;  peritonitis, 
273;  pneumonia,  273;  pylorospasm, 
284;  pyloric  stenosis,  275;  tonsillitis, 
278; 

— in  the  isolated  stomach,  160; 

— influence  of,  on  circulation,  88;  on  re- 
flexes, 85;  on  salivation,  89; 

— influence  on,  by  chemicals  in  the 
mouth,  161, 166;  chemicals  in  the  stom- 
ach, 171;  decerebration,  149;  diabetic 
blood,  221;  starvation  blood,  219; 
section  of  stomach  nerves,  158; 

— rnechanism  of,  169,  183;  relation  of,  to 
digestion  contractions,  56;  to  feeding 
habits,  153, 185. 

Gastric  juice:  auto-digestion  of,  235; 
chemistry  of,  248;  quantity  of,  243, 
245;  secretion  of,  233,  240. 

Gastric  mucosa:  pain  sensation  from, 
102;  tactile  sensation  from,  103;  tem- 
perature sensation  from,  104;  sensa- 
tion of  nausea  from,  113. 

Gastric  tonus:  relation  of,  to  hunger,  67; 
in  prolonged  starvation,  128,  141. 

Gastric  ulcer,  hunger  in,  264. 

Gastritis,  hunger  in,  278. 

Haller,  theory  of,  hunger,  17. 

Headache,  in  hunger,  92,  94,  134. 

Hemorrhage,  influence  of,  on  hunger,  222. 

Herbivora,  hunger  in,  41,  48,  50. 

Hertz,  work  of,  on  sensibility  of  stomach, 
103,  105,  III,  264. 

Hunger:  cause  of,  61;  general  phenom- 
ena of,  7;  influence  of,  on  behavior,  8, 
134, 136, 144, 147;  in  disease  conditions, 
261;  in  higher  animals,  6,  30,  125;  in 
plants,  5;  in  protozoa,  i;  method  of 
objective  study  of,  31;  relation  of,  to 
appetite,  96;  relation  of,  to  the  need  of 
food,  22,  153,  185;   theories  of,  16. 

Hunger  centers:  in  cerebrum,  216;  in 
medulla,  214;  in  optic  thalami,  215. 

Hunger  pains:   in  gastric  ulcer,  263,  281. 

Hunger  tetanus  of  stomach:  in  dogs,  44; 
in  man,  37,  65,  212;  in  pancreatic  dia- 
betes, 268;  in  prolonged  starvation,  125; 
in  pyloric  stenosis,  275. 

Hydrochloric  acid,  role  of,  in  hunger  pains, 
264. 

Hyperacidity,  in  stomach,  256. 


Infants:  feeding  of,  121;  hunger  of,  40, 
119. 

Inheritance:  of  chemotropic  elements  of 
appetite,  n,  99;  of  feeding  reflexes, 
9,  12. 

Inhibition  of  hunger:  by  bitter  tonics, 
292;  by  cold  stimulation  of  the  skin, 
206,  211;  by  disease,  261;  by  the  emo- 
tions, 151,  182;  by  heat  stimulation  of 
the  skin,  206;  by  mastication,  165; 
by  running,  210;  by  sapid  substances 
in  the  mouth,  160,  167,  189,  193;  by 
smoking,  199;  by  stimulation  of  gastric 
rnucosa,  169;  by  stimulation  of  intes- 
tinal mucosa,  194;  by  swallowing,  167. 

Instincts,  relation  of,  to  hunger  and  appe- 
tite, 9, 

Intestines,  contractions  of,  in  hunger,  81. 

Luckhardt,  work  of,  on  hunger,  220,  222, 
230,  268,  271,  277,  280. 

Mange,  increased  hunger  in,  268. 
Mastication,  inhibition  of  hunger  by,  165. 
Medulla,  hunger  centers  in,  210. 
Memory,  in  appetite,  97. 
Moorhead,  work  of,  on  bitters,  299,  300. 

Nausea:     in  prolonged  starvation,   135; 

relation  of,  to  hunger,  7,  92,  94,  113. 
Nicolai,  work  of,  on  hunger,  25. 

Optic  thalami,  role  of,  in  hunger,  154,  215. 

Pancreatic  diabetes,  hunger  in,  268. 
Parathyroid  tetany,  hunger  in,  273. 
Paroexia,  267. 

Patterson,  work  of,  on  hunger,  52,  120, 
123. 

Pepsin,  concentration  of,  in  gastric  juice, 

259- 
Peritonitis,  hunger  in,  273. 

Phagocytosis,  in  protozoa,  influence  of 

hunger  on,  3,  4. 
Phlorhizin  glucosuria,  230. 
Physical  exercise,  effect  of,  on  hunger, 

203,  205,  210. 
Pituitrin,  influence  of,  on  hunger,  229. 
Plants,  hunger  in,  5. 
Pneumonia,  hunger  and  appetite  in,  273. 


INDEX 


319 


Polyphagia:  in  man,  266;  in  mange,  269; 
in  pancreatic  diabetes,  268. 

Pressure  on  abdomen,  effect  of,  on  hun- 
ger, 200. 

Protozoa,  hunger  behavior  of,  2,  4. 

Pyloric  stenosis,  influence  of,  on  hunger, 
275. 

Pylorospasm,  hunger  contractions  in,  284. 

Pylorus,  effect  of  patency  of,  on  hunger, 
23- 

Rectal  feeding,  influence  of,  on  hunger, 

25- 
Rogers,  work  of,  on  hunger,  51,  56,  143, 

151,  154,  194,  215. 
Rumen,  hunger  contractions  of,  50. 
Ruminants,  hunger  in,  50. 

Salivation,  in  hunger,  89. 

Salt  hunger,  14. 

Satiety, .origin  of  sensation  of,  in. 

Sleep,  hunger  contractions  in,  150, 

Smoking,  influence  of,  on  hunger,  199. 

Splanchnic  nerves,  effect  of  section  of,  on 
hunger,  155. 

Starvation:  after-effects  of,  137;  dis- 
comforts of,  138;  gastric  hunger  con- 
tractions in,  126;  gastric  juice  in,  128; 
gastric  tonus  in,  26,  141;  hunger  and 
appetite  in,  125,  134;  literature  on, 
144. 


Starvation  blood,  influence  of,  on  hunger, 
219. 

Stomach:  action  of  bitter  tonics  on,  289; 
digestion  contractions  of,  55;  extirpa- 
tion of,  in  relation  to  hunger,  23 ;  fluid 
content  of  empty  stomach,  232;  hun- 
ger contractions  of,  in  amphibia  and 
reptilia,  53;  in  birds,  51;  in  dogs,  41; 
in  herbivora,  48;  in  infants,  40;  in 
man,  36;  sensibility  of,  to  appetite,  99, 
115;  to  pain,  102;  to  temperature,  104; 
to  touch,  103. 

Stomach  pouch  (Pavlov),  hunger  contrac- 
tions of,  225. 

Stomach  pulse,  39. 

Taste  sense:  influence  of,  on  hunger,  163; 
importance  of,  in  appetite  secretion, 
235,  240,  247;  role  of,  in  appetite,  98. 

Thirst,  lack  of  appetite  elements  in,  13. 

Tonsillitis,  hunger  and  appetite  in,  278. 

Vagi  centers,  in  medulla:  reflex  control 
of,  169,  210,  218;  tonus  of,  206,  214. 

Vagi  nerves :  effect  of  section  of,  on  hun- 
ger contractions,  156;  relation  to 
hunger  sense,  22,  214;  role  of,  in  gastric 
juice  secretion,  234. 

Water  in  stomach,  influence  of,  on  hun- 
ger,  171. 

Weakness,  feeling  of,  in  hunger,  7,  92, 
135,  137. 


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Control  of 


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]iealth  and  disease* 


lunger   in 


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